颅骨骨折在脑外伤促新骨形成过程中的作用及机制研究
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摘要
临床工作中发现伴有脑外伤的骨折病人,其骨痂生长明显增多加快,甚至在某些关节周围出现异位骨化。关于此现象国内外均有临床报道和基础研究,提出了很多假说,但其中机制迄今仍不明朗。目前提出的机制多数是针对脑外伤后是否会导致脑组织内某些成份释放入血液系统促进新骨形成,但没有关于颅骨骨折是否会引起颅骨中的某些成分进入血液系统促进新骨形成的研究和报道。
目的:
探讨颅骨骨折在脑外伤促新骨形成过程中的作用;研究颅骨骨折伴股骨骨折组大鼠血浆对骨髓间质细胞的作用;研究颅骨移植对骨折愈合的影响作用;研究IGFBP-5在颅骨组织中的表达情况,及其对骨髓间质细胞的作用。
方法:
研究分以下几个部分进行:
1.建立实验动物模型,比较颅骨骨折伴股骨骨折、脑外伤伴股骨骨折及单纯股骨骨折后骨折愈合的情况。
2.进行大鼠骨髓间充质干细胞的分离、培养、纯化及鉴定。
3.比较颅骨骨折组血浆、脑外伤组血浆及单纯骨折组血浆对大鼠骨髓间充质细胞增殖、分化及矿化功能的影响;比较颅骨浸泡液、髂骨浸泡液对大鼠骨髓间充质细胞增殖、分化及矿化功能的影响。
4.研究IGFBP-5在颅骨、髂骨及股骨中的表达,比较不同浓度IGFBP-5对大鼠骨髓间充质细胞增殖、分化及矿化功能的影响;去除脑外伤组血浆中的IGFBP-5,比较其与未处理脑外伤组血浆对大鼠骨髓间充质细胞增殖、分化及矿化功能的影响。
结果:
1.通过建立脑外伤、颅骨骨折及股骨骨折动物模型,实验结果显示术后4周颅骨骨折组生成骨痂体积比单纯骨折组骨痂大(P<0.05),但小于脑外伤组(P<0.05);骨折断端骨密度检测结果显示颅骨骨折组与颅脑损伤组无明显差异(P>0.05),但两组都低于单纯骨折组(P<0.05);组织形态学HE染色显示颅骨骨折组与脑外伤组类似,但不同与单纯骨折组。
2.采用密度梯度离心法和贴壁筛选法相结合,利用Ficoll分离液能有效地将大部分造血细胞和单个核细胞分离开来,再经过体外贴壁培养,去除悬浮生长的造血系细胞,所获得的BMSCs纯度高且活性强。
3.颅骨移植组骨痂体积明显大于髂骨移植(P<0.05)和单纯骨折组(P<0.05)。骨折断端骨密度检测结果显示颅骨移植组低于单纯骨折组及髂骨移植组(P<0.05);组织形态学HE染色显示颅骨移植组不同于髂骨移植组和单纯骨折组; CBF+F血浆组细胞在增殖、向成骨细胞分化及促进钙结节生成能力均较F组血浆培养组强,二者比较有统计学差异(P<0.05),但较TBI+F动物血浆培养组数量差,二者比较有统计学差异(P<0.05);颅骨浸泡液在增殖、向成骨细胞分化及促进钙结节生成能力三方面均较髂骨浸泡液强(P<0.05)。
4.各骨折组动物模型血浆中IGFBP-5浓度于骨折后第8小时达到高峰,此后逐渐减低,至术后第5天时,各组血浆IGFBP-5浓度与正常组血浆无差别。骨折后8小时CBF+F组血浆IGFBP-5浓度是单纯骨折组血浆IGFBP-5浓度的2.83倍,是正常大鼠血浆IGFBP-5浓度的3.12倍。
结论:
1.颅骨骨折可促进新骨形成,颅骨骨折在脑外伤促新骨形成过程中起着重要作用。
2.颅骨移植促进新骨形成作用强于髂骨移植。
3. IGFBP-5在颅骨中高表达,且具有促BMSCs增殖、向成骨细胞分化及钙化的作用,在颅骨骨折促新骨形成过程中起着重要作用。
There is a common clinical phenomenon: if a fractured patient has traumatic brain injury (TBI) at the same time, his fracture healing process will be accelerated and heterotopic ossification can be found near some joint. There were some clinical reports and experimental studies about this phenomenon. Lots of hypotheses were made but the mechanism of this phenomenon isn' t clear so far. Most of hypotheses aimed at whether brain components be released after traumatic brain injury and some factors that can accelerate the fracture healing were in it. But no hypotheses and study aimed at whether cranial bone components be released after traumatic brain injury and some factors that can accelerate the fracture healing.
Purpose:
To explore the function and mechanism of cranial bone fracture in accelerated new bone forming combined with traumatic brain injury. To study the effect of blood plasma derived from rats with traumatic brain injury and femur fracture on the BMSCs. To explore the effect of cranial bone transplantation on fracture healing. To study the expression of IGFBP-5 in cranial bones and the effect of it on BMSCs proliferation, differentiation and mineralization.
Methods:
The research can be divided into 4 parts below:
1. To compare the effect of cranial bone fracture, traumatic brain injury on fracture healing after constructing animal model.
2. Explore the methods of isolation, purification, culture and identification of BMSCs.
3. Compare the effect of blood plasma extracted from the rats of CBF+F group, TBI+F group and F group on BMSCs proliferation, differentiation, and mineralization. Compare the effect of soaked liquid of cranial bone and iliac bone on BMSCs proliferation, differentiation, and mineralization.
4. Explore the expression of IGFBP-5 in cranial bone, iliac bone and femur. Compare the effect of different IGFBP-5 content on BMSCs proliferation, differentiation and mineralization. Remove IGFBP-5 of TBI+F blood plasma and compare the effect of this blood plasma with common TBI+F blood plasma on BMSCs proliferation, differentiation and mineralization.
Result:
After constructing animal model, the 4-week callus volume of CBF+F group is larger than simple fracture group(P<0.05),but minor than TBI+F group(P<0.05). The bone density and the biomechanics results of callus demonstrate that there was no statistics difference between the CBF+F group and TBI+F group(P>0.05). But the results of these two group were minor than simple fracture group (P<0.05). The HE stain results of callus showed that CBF+F group were similar to TBI+F group in histomorphology and they had more difference comparing with the simple fracture group. The blood plasma derived from the rats of CBF+F group had more powerful stimulating ability in BMSCs proliferation, differentiation, and mineralization than F group(P<0.05), but had less stimulating ability than TBI+F group(P<0.05). The soaked liquid of cranial bones had had more powerful stimulating ability in BMSCs proliferation, differentiation, and mineralization than soakedliquid of iliac bone group(P<0.05). The IGFBP-5 contents of the animal models were peaked at 8 hours after surgery and decreased stepwise. There were no significant difference between surgery groups and normal rats at 5 days after surgery. The IGFBP-5 content of CBF+F group was 2.83 times as simple fracture group and 3.12 times as normal group.
Conclusion:
1. Cranial bones fracture can stimulate new bone forming and it was important factor in TBI accelerating new bone forming.
2. The cranial bones transplantation have more powerful ability in accelerating new bone forming than iliac bone transplantation.
3. IGFBP-5 were mostly exist in cranial bones and it has powerful stimulating ability in BMSCs proliferation, differentiation, and mineralization. IGFBP-5 is one important factor in TBI accelerating new bone forming.
目的:
探讨颅骨骨折在脑外伤促新骨形成过程中的作用;研究颅骨骨折伴股骨骨折组大鼠血浆对骨髓间质细胞的作用;研究颅骨移植对骨折愈合的影响作用;研究IGFBP-5在颅骨组织中的表达情况,及其对骨髓间质细胞的作用。
方法:
研究分以下几个部分进行:
1.建立实验动物模型,比较颅骨骨折伴股骨骨折、脑外伤伴股骨骨折及单纯股骨骨折后骨折愈合的情况。
2.进行大鼠骨髓间充质干细胞的分离、培养、纯化及鉴定。
3.比较颅骨骨折组血浆、脑外伤组血浆及单纯骨折组血浆对大鼠骨髓间充质细胞增殖、分化及矿化功能的影响;比较颅骨浸泡液、髂骨浸泡液对大鼠骨髓间充质细胞增殖、分化及矿化功能的影响。
4.研究IGFBP-5在颅骨、髂骨及股骨中的表达,比较不同浓度IGFBP-5对大鼠骨髓间充质细胞增殖、分化及矿化功能的影响;去除脑外伤组血浆中的IGFBP-5,比较其与未处理脑外伤组血浆对大鼠骨髓间充质细胞增殖、分化及矿化功能的影响。
结果:
1.通过建立脑外伤、颅骨骨折及股骨骨折动物模型,实验结果显示术后4周颅骨骨折组生成骨痂体积比单纯骨折组骨痂大(P<0.05),但小于脑外伤组(P<0.05);骨折断端骨密度检测结果显示颅骨骨折组与颅脑损伤组无明显差异(P>0.05),但两组都低于单纯骨折组(P<0.05);组织形态学HE染色显示颅骨骨折组与脑外伤组类似,但不同与单纯骨折组。
2.采用密度梯度离心法和贴壁筛选法相结合,利用Ficoll分离液能有效地将大部分造血细胞和单个核细胞分离开来,再经过体外贴壁培养,去除悬浮生长的造血系细胞,所获得的BMSCs纯度高且活性强。
3.颅骨移植组骨痂体积明显大于髂骨移植(P<0.05)和单纯骨折组(P<0.05)。骨折断端骨密度检测结果显示颅骨移植组低于单纯骨折组及髂骨移植组(P<0.05);组织形态学HE染色显示颅骨移植组不同于髂骨移植组和单纯骨折组; CBF+F血浆组细胞在增殖、向成骨细胞分化及促进钙结节生成能力均较F组血浆培养组强,二者比较有统计学差异(P<0.05),但较TBI+F动物血浆培养组数量差,二者比较有统计学差异(P<0.05);颅骨浸泡液在增殖、向成骨细胞分化及促进钙结节生成能力三方面均较髂骨浸泡液强(P<0.05)。
4.各骨折组动物模型血浆中IGFBP-5浓度于骨折后第8小时达到高峰,此后逐渐减低,至术后第5天时,各组血浆IGFBP-5浓度与正常组血浆无差别。骨折后8小时CBF+F组血浆IGFBP-5浓度是单纯骨折组血浆IGFBP-5浓度的2.83倍,是正常大鼠血浆IGFBP-5浓度的3.12倍。
结论:
1.颅骨骨折可促进新骨形成,颅骨骨折在脑外伤促新骨形成过程中起着重要作用。
2.颅骨移植促进新骨形成作用强于髂骨移植。
3. IGFBP-5在颅骨中高表达,且具有促BMSCs增殖、向成骨细胞分化及钙化的作用,在颅骨骨折促新骨形成过程中起着重要作用。
There is a common clinical phenomenon: if a fractured patient has traumatic brain injury (TBI) at the same time, his fracture healing process will be accelerated and heterotopic ossification can be found near some joint. There were some clinical reports and experimental studies about this phenomenon. Lots of hypotheses were made but the mechanism of this phenomenon isn' t clear so far. Most of hypotheses aimed at whether brain components be released after traumatic brain injury and some factors that can accelerate the fracture healing were in it. But no hypotheses and study aimed at whether cranial bone components be released after traumatic brain injury and some factors that can accelerate the fracture healing.
Purpose:
To explore the function and mechanism of cranial bone fracture in accelerated new bone forming combined with traumatic brain injury. To study the effect of blood plasma derived from rats with traumatic brain injury and femur fracture on the BMSCs. To explore the effect of cranial bone transplantation on fracture healing. To study the expression of IGFBP-5 in cranial bones and the effect of it on BMSCs proliferation, differentiation and mineralization.
Methods:
The research can be divided into 4 parts below:
1. To compare the effect of cranial bone fracture, traumatic brain injury on fracture healing after constructing animal model.
2. Explore the methods of isolation, purification, culture and identification of BMSCs.
3. Compare the effect of blood plasma extracted from the rats of CBF+F group, TBI+F group and F group on BMSCs proliferation, differentiation, and mineralization. Compare the effect of soaked liquid of cranial bone and iliac bone on BMSCs proliferation, differentiation, and mineralization.
4. Explore the expression of IGFBP-5 in cranial bone, iliac bone and femur. Compare the effect of different IGFBP-5 content on BMSCs proliferation, differentiation and mineralization. Remove IGFBP-5 of TBI+F blood plasma and compare the effect of this blood plasma with common TBI+F blood plasma on BMSCs proliferation, differentiation and mineralization.
Result:
After constructing animal model, the 4-week callus volume of CBF+F group is larger than simple fracture group(P<0.05),but minor than TBI+F group(P<0.05). The bone density and the biomechanics results of callus demonstrate that there was no statistics difference between the CBF+F group and TBI+F group(P>0.05). But the results of these two group were minor than simple fracture group (P<0.05). The HE stain results of callus showed that CBF+F group were similar to TBI+F group in histomorphology and they had more difference comparing with the simple fracture group. The blood plasma derived from the rats of CBF+F group had more powerful stimulating ability in BMSCs proliferation, differentiation, and mineralization than F group(P<0.05), but had less stimulating ability than TBI+F group(P<0.05). The soaked liquid of cranial bones had had more powerful stimulating ability in BMSCs proliferation, differentiation, and mineralization than soakedliquid of iliac bone group(P<0.05). The IGFBP-5 contents of the animal models were peaked at 8 hours after surgery and decreased stepwise. There were no significant difference between surgery groups and normal rats at 5 days after surgery. The IGFBP-5 content of CBF+F group was 2.83 times as simple fracture group and 3.12 times as normal group.
Conclusion:
1. Cranial bones fracture can stimulate new bone forming and it was important factor in TBI accelerating new bone forming.
2. The cranial bones transplantation have more powerful ability in accelerating new bone forming than iliac bone transplantation.
3. IGFBP-5 were mostly exist in cranial bones and it has powerful stimulating ability in BMSCs proliferation, differentiation, and mineralization. IGFBP-5 is one important factor in TBI accelerating new bone forming.
引文
1. Gibson JMC.Multiple injuries:management of the patient with a fracturedfemur and a head injury.J Bone Joint Surg(Sr),1960,42(3):425
2. Bidner SM, Rubins IM, Desjardins JV, Zukor DJ, Goltzman D. Evidence for a humoral mechanism for enhanced osteogenesis after head injury. J Bone Joint Surg Am 1990; 72:1144-9.
3. Newman RJ, Stone MH, Mukherjee SK. Accelerated fracture union in association with severe head injury. Injury 1987;18:241
4. Perkins R, Skirving AP. Callus formation and the rate of healing of femoral fractures in patients with head injuries. J Bone Joint Surg Br 1987; 69:521-4.
5. Khare GN,Gautam VK,Gupta LN ,el a1.A new hypothesis for faster healing of fractures in hem injured patients.Indian J Med Sci,1995,49(2):281
6. Wildburger R, Zarkovic N, Egger G, PetekW, Zarkovic K, Hofer HP. Basic fibroblast growth factor (BFGF) immunoreactivity as a possible link between head injury and impaired bone fracture healing. Bone Miner 1994; 27:183-92.
7. Wildburger R, Zarkovic N, Egger G, et al. Comparison of the values of basic fibroblast growth factor determined by an immunoassay in the sera of patients with traumatic brain injury and enhanced osteogenesis and the effects of the same sera on the fibroblast growth in vitro. Eur J Clin Chem Clin Biochem 1995; 33:693-8.
8. Mohan S, Nakao Y, Honda Y, Landale E, Leser U, Dony C,Lang K, Baylink DJ . Studies on the mechanisms by which insulin-like growth factor binding protein (IGFBP-4) and IGFBP-5 modulate IGF actions in bone cells. J Biol Chem. 1995; 270:20424-20431
9. Richman C, Baylink DJ, Lang K, Dony C, Mohan S. Recombinant human insulin-like growth factor binding protein-5 (rhIGFBP-5) stimulates bone formation parameters in vitro and in vivo. Endocrinology.1999; 140:4699-470
10. Miyakoshi N, Richman C, Kasukawa Y, Linkhart TA, Baylink DJB, Mohan S. Evidence that IGF-binding protein-5 functions as a growth factor. J Clin Invest.2001; 107:73-81
11. Conover CA. Regulation and physiological role of insulin-like growth factor binding proteins. Endocr J.1996; 43(Suppl): 43-48
1. Gibson JMC.Multiple injuries:management of the patient with a fractured femur and a head injury.J Bone Joint Surg,1960,42(3):425
2. Spencer RF.The effect of head injury on fracture healing:A quantitative assessment.J Bone Joint Surg,1987.69(4):525
3. Perkins R,Skirving AP.Callus formation and the rate of healing of femoral fractures in patients with head injuries.Journal of Bone and Joint Surgery(British volume), 1987,69:521-524
4. Feeney DM,Boyeson MG,Linn RT,et a1.Responses to cortical injury: Methodology and local effects of contusions in the rat.Brain Res,1981,211:67-77
5. Lighthal JW, Dixon CE, Anderson TE, et al. Experimental models of brain injury. Neurotrauma, 1989, 6:83-97.
6. Gennarelli TA. Mechanisms of brain injury. J Emerg Med, 1993, 11:5.
7. Carbonel l WS, Maris DO, McCall T, et al. Adaptation of the fluid percussion injury model to the mouse. Neurotrauma, 1998, 15:217-229.
8. Sanders MJ, Dietrich WD, Green EJ. Cognitive function following traumatic brain injury: effects of injury severity and recovery period in a parasagittal fluid-percussive injury modeI.J Neurotrauma, 1999, 16: 915-925.
9. DeRoss AL Adams JE, Vane DW, et al. Multiple head injuries in rats:effects on behavior. Trauma.2002, 52:708-714.
10.扬卫红,林敬明,马伯扬,等.大鼠脑冷冻伤引起的脑水肿模型的改进.神经解剖杂志,1999, 15: 299-300
11. Erdincler P,Tuzgen S,Erdincler ED,et al.Influence of aging on hlood-hrain harrier permeability and free radical Formation following experimentalbrain cold injury. Acta Neurochir, 2002, 144:195-199.
12. Nag S. The hIood-hrain harrier and cerebral angiogenesis: Iesions from the cold-injury model. Trends Mol Med, 2002,8:38-49.
13. Garland DE, Rothi B, Waters RL. Femoral fractures in headinjuries adults. Clin Orthop 1982; 219-25.
14.Garland DE, Toder L. Fractures of the tibial diaphysis in adults with head injuries. Clin Orthop 1980; 198-202.
1. Castro RF,Jackson KA,Goodell MA et al.F ailure of bone marrow cells to Transdifferentiate into neural cells in vivo.Science.2002;297:1299
2. Mezey E ,Nagy A ,Szalayova I et al .C omment on“Failure of bone marrow Cells to t ransdiferentiate into neural cell vivo”.Science.2003;299:1184
3. BlauH, BrazeltonT, Keshet G, Rossi F. Something in the eye of the beholder. Science.2002;298:361-362
4. Bobis S, Jarocha D, Majka M. Mesenchymal stem cells: characteristics and clinical applications. Folia Histochem Cytobiol. 2006, 44(4): 215-30
5. Blancor P, Rimiunccib M, Gronthosc S, et al. Bone marrow stromal stem cells:nature, biology and potential applications. Stem Cell, 2001,19(3):180-192
6. Tang Y, Wang R, Zhang C, et al. In vitro differentiation of rat bone mesenchymal stem cells into neuron-like cells induced by vitamin A acid etc. Sichuan Da Xue Xue Bao Yi Xue Ban, 2003, 34:377-80.
7. Frank P, Barrry J, Mary Murphy. Mesenchymal stem cells clinical applications and biological characterization. The International Journal of Biochemistry and Cell Biology.2004,36:568-584
8. Nuttall ME, Patton AJ, et al.Human trabecullar bone cells are able to express both osteoblastic and adipocytic phenotype: implications for osteopenic disorders. J Bone Miner Res, 1998, 13:371-382.
9. Zohar P, Sodek J, McCulloch CA. Characterization of stromal progenitor cells enriched by flow cytometry. Blood. 1997; 90:3471-3481.
10. Herbertson A, Aubin JE. Cell sorting enriches osteogenic populations in rat bone marrow stromal cell cultures. Bone. 1997; 21:491-560.
11. Friedenstein A J, Chailakhyan R K, Gerasimov U V. Bone marrow osteogenic stem cells: in vitro cultivation and transplantation in difusionchambers.Cel Tissue Kinet, 1987,20: 263-72.
12. 1 Pittenger M F, Mackay AM, Beck SC, et al. MuldGneage potential of adult humanmesenchymal stem cells. Science, 1999, 284: 143-147
13. JiangY, JahagirdarBN, Reinhardt RL, et al. Pluripotency of mesenchymal stem cells derived from adult marrow. Nature, 2002, 418 (6893): 41
14. Tocci A, Forte L. Mesenchymal stem cell: use and perspectives. The hematology journal: the official journal of the European Haematology Association / EHA 2003; 4(2):92-6.
15. Kadiyala S, Young RG, Thiede MA, Bruder SP. Culture expanded canine mesenchymal stem cells possess osteochondrogenic potential in vivo and in vitro. Cell transplantation 1997; 6(2):125-34.
16. Friedenstein AJ. Precursor cells of mechanocytes. International review of cytology 1976; 47:327-59.
17. Nagatomo K, Komaki M, Sekiya I, Sakaguchi Y, Noguchi K, Oda S. Stem cell properties of human periodontal ligament cells. Journal of periodontal research 2006; 41(4):303-10.
18. Lorenz MR, Holzapfel V, Musyanovych A, Nothelfer K, Walther P, Frank H. Uptake of functionalized, fluorescent-labeled polymeric particles in different cell lines and stem cells. Biomaterials 2006; 27(14):2820-8.
19. Kotobuki N, Hirose M, Machida H, Katou Y, Muraki K, Takakura Y. Viability and osteogenic potential of cryopreserved human bone marrow-derived mesenchymal cells. Tissue engineering 2005; 11(5-6):663-73.
20. Fukuchi Y, Nakajima H, Sugiyama D, Hirose I, Kitamura T, Tsuji K. Human placenta-derived cells have mesenchymal stem/progenitor cell potential. Stem cells, 2004; 22(5):649-58.
21. Fortier LA, Nixon AJ, Williams J. Isolation and chondrocytic differentiation of equine bone marrow derived mesenchymal stem cells. Am J Vet Res, 1998, 59:1182-1187.
22.司徒镇强,吴军正,单立冬,杨天明等.差速贴壁法分离培养早期人胚胎骨髓间充质干细胞.东南大学学报,2005,24(4):218-221.
23 Pitienger MF, Mackay AM, Beck SC, et al. Multilineage potential of adult human mesenchymal stem cells. Science.1999,284(5411):143-147。
1. Feeney DM,Boyeson MG,Linn RT,et a1.Responses to cortical injury:I Methodology and local effects of contusions in the rat.Brain Res,1981,21 1:67-7
2. Perkins R,Skirving AP.Callus formation and the rate of healing of femoral fractures in patients with head injuries.Journal of Bone and Joint Surgery(British volume) 1987;69:521-52
3. Markowitz NR, Cranial bone grafting in oral and maxillofacial surgery J Am Dent Assoc, Jul 1992; 123: 206-211.
4. Zins JE, Whitaker LA, Membranous versus endochondral bone:implications for craniofacial reconstruction. Plast Reconstr Surg,1983,72:778.
5. Kusak JF,Zins JE.Whitaker LA. The early revascularization of membranous bone. Plast Reconstr Surg,1985,76:510
6. Donovan MG,Dickerson NC,Hellstein JW, et al. Autologous calvarial and ilac onlay bone grafts in miniature swine. J Oral Maxillofac Surg 1993.51:898
7. Celik MR.A simple method for cranial bone chip harvesting.Ann Plast-Surg,2003,51(4):434-435
8. Fearen JA.AMagneticResonanceImesing Investigation of Potential Subolinieal Complications after in Situ Cranial Bone Graft Han'est.Plastic&BeconstructiveSurgery,200O,105(6):1935-1939
9. Melega JM.Cranial Bone Graft for the Maxillary Sinus Floor.Plastic and Reconstructive Surgery,2003.111(2):972
1. Mohan S, Nakao Y, Honda Y, Landale E, Leser U, Dony C,Lang K, Baylink DJ (1995) Studies on the mechanisms by which insulin-like growth factor binding protein (IGFBP-4) and IGFBP-5 modulate IGF actions in bone cells. J Biol Chem 270:20424–20431
2. Richman C, Baylink DJ, Lang K, Dony C, Mohan S. Recombinant human insulin-like growth factor binding protein-5 (rhIGFBP-5) stimulates bone formation parameters in vitro and in vivo. Endocrinology.1999.140:4699–470
3. Miyakoshi N, Richman C, Kasukawa Y, Linkhart TA, Baylink DJB, Mohan S. Evidence that IGF-binding protein-5 functions as a growth factor. J Clin Invest 2001.107:73–81
4. Conover CA. Regulation and physiological role of insulin-like growth factor binding proteins. Endocr J.1996.43 (Suppl): 43-48
5. Feeney DM,Boyeson MG,Linn RT,et a1.Responses to cortical injury:I Methodology and local effects of contusions in the rat.Brain Res,1981,21:67-77
1. Gibson JMC.Multiple injuries:management of the patient with a fracturedfemur and a head injury.J Bone Joint Surg(Sr),1960,42(3):425
2. Bidner SM, Rubins IM, Desjardins JV, Zukor DJ, Goltzman D. Evidence for a humoral mechanism for enhanced osteogenesis after head injury. J Bone Joint Surg Am 1990; 72:1144-9.
3. Newman RJ, Stone MH, Mukherjee SK. Accelerated fracture union in association with severe head injury. Injury 1987;18:241
4. Perkins R, Skirving AP. Callus formation and the rate of healing of femoral fractures in patients with head injuries. J Bone Joint Surg Br 1987; 69:521-4.
5. Roberts Heterotopic ossification complicating paralysis of intracranial origin. J Bone Joint Surg Br 1968;50-B:70-7.
6. Citta-Pietrolungo TJ, Alexander MA, Steg NL. Early detection of heterotopic ossification in young patients with traumatic brain injury. Arch Phys Med Rehabil 1992; 73:258-62.
7. Smith R. Head injury, fracture healing and callus. J Bone Joint Surg Br 1987; 69:518—20.
8. Spencer RF. The effect of head injury on fracture healing. A quantitative assessment. J Bone Joint Surg Br 1987; 69:525-8.
9. Boulet M, Marier JR. Precipitation of calcium phosphates from solution at near physiological concentration. Arch Biochem 1961; 93:157.
10. Wildburger R,Zarkovic N,Tonkovic G,et a1.Post- traumatic hormonal disturbances:pmlactin as a link between head injury and enhanced osteogenesis.J Endocrinol Invest,1998,21(1):78
11. Khare GN,Gautam VK,Gupta LN ,el a1.A new hypothesis for faster healing of fractures in hem injured patients.Indian J Med Sci,1995,49(2):281
12. Dewulf N,Verschuren K,Lonnoy O,Moren A,et a1. Distinct spatial and temporal expression patterns of two type I receptors for bone morphogenic proteins during mouse embryiogenesis.Endoerinology,1995,136(12):2652
13. Scherbel U,Riess P,Khurana JS,et a1.Expression of Bone Marphogenic Proteins in Rats with and without Brain lnjnry and a Tibia Fracture.The University of Pennsylvania Orthopaedic Journa1.2001,14(1):85
14. Yaoita H,Orimo H,Shirai Y. Shimada T. Expression of bone morphogenic proteins less homolog genes following rat femoral fracture.J Bone Miuer Metab 2000,18(1):63
15. Walter HJ,Berry M,Hill DJ,et a1.Sptial and temporal changes in the insulin-like growth factor(1GF)axis indicate autoefine/paracfine action ofIGF-1 within wounds ofthe brain.Endocrinology. 1997,138(7):3024
16. Beeton CA,Brooks RA,Rushton N.Circulating levels of insulin- like growth factor
1 and insulin-like growth factor binding protein-3 in patients with severe head injury.J Bone Joint Surg(Br),2002,84(3):434
17. Brinker MR, Miller MD. Basic sciences: bone injury and repair. In: Miller M, editor. Review of Orthopaedics. 3rd ed. Saunders WB; 2000. p. 19-22.
18. Wildburger R, Zarkovic N, Egger G, PetekW, Zarkovic K, Hofer HP. Basic fibroblast growth factor (BFGF) immunoreactivity as a possible link between head injury and impaired bone fracture healing. Bone Miner 1994; 27:183-92.
19. Wildburger R, Zarkovic N, Egger G, et al. Comparison of the values of basic fibroblast growth factor determined by an immunoassay in the sera of patients with traumatic brain injury and enhanced osteogenesis and the effects of the same sera on the fibroblast growth in vitro. Eur J Clin Chem Clin Biochem 1995; 33:693-8.
20.汪学军,裴福兴,池雷霆,等.骨折合并脑外伤时骨愈合过程中bFGF作用的实验研究.中华骨科杂志,2003,23(1):5
21. Malcangio M,Garrett NE,Tomlinson DR.Nerve growth factor treatment increases stimulus-evoked re]ease of sensory neuropep-tides in the rat Spinal Cord.Eur JNeurosci,1997,9(6):101
22. Grills BL.Schuijers JA,Ward AR.Topical application of new growth factor improves fracture healing in rats.J Orthop Res,1997.15(3):235
23. Madsen JE. Hukkanen M.Aune AK.et 81.Fraetune healing and callus innervation after peripheral nerve resection in rats.Clin Orthop.1998,351(2):230
24. Konttinen Y'F,Imai S,Suda A.Neuropeptides an d the puzzle of bone remodeling.Acta Ohop Scand,1996. 67(4):63
25. Shih C,Bernard GW .Neurogenie substance P stimulates osteoganesis in vitro.Peptides,1997. 18(3):323
26. Rameshwar P,Gascon P.Substance P(SP)mediates production of stem cell factor and interleukin-1 in bone mTOW strnma:Potential autoregulatory role for these cytokines in SP receptor expression and induction.Blood,1995.86(3):482
27. Vignery A.McCarthy. The neuropeptide calcitonin gene-related peptlde stimulates insulin—like growth factor I production by primary fetal rat ostooblasts.Bone,1996,18(2):33
28. Garland DE, Rothi B, Waters RL. Femoral fractures in headinjuries adults. Clin Orthop 1982;219-25.
29. Garland DE, Toder L. Fractures of the tibial diaphysis in adults with head injuries. Clin Orthop 1980; 198-202.
30. Garland DE, Dowling V. Forearm fractures in the head-injured adult. Clin Orthop 1983; 176:190-6.
31. Kushwaha VP, Garland DG. Extremity fractures in the patient with a traumatic brain injury. J Am Acad Orthop Surg 1998; 6:298-307.
2. Bidner SM, Rubins IM, Desjardins JV, Zukor DJ, Goltzman D. Evidence for a humoral mechanism for enhanced osteogenesis after head injury. J Bone Joint Surg Am 1990; 72:1144-9.
3. Newman RJ, Stone MH, Mukherjee SK. Accelerated fracture union in association with severe head injury. Injury 1987;18:241
4. Perkins R, Skirving AP. Callus formation and the rate of healing of femoral fractures in patients with head injuries. J Bone Joint Surg Br 1987; 69:521-4.
5. Khare GN,Gautam VK,Gupta LN ,el a1.A new hypothesis for faster healing of fractures in hem injured patients.Indian J Med Sci,1995,49(2):281
6. Wildburger R, Zarkovic N, Egger G, PetekW, Zarkovic K, Hofer HP. Basic fibroblast growth factor (BFGF) immunoreactivity as a possible link between head injury and impaired bone fracture healing. Bone Miner 1994; 27:183-92.
7. Wildburger R, Zarkovic N, Egger G, et al. Comparison of the values of basic fibroblast growth factor determined by an immunoassay in the sera of patients with traumatic brain injury and enhanced osteogenesis and the effects of the same sera on the fibroblast growth in vitro. Eur J Clin Chem Clin Biochem 1995; 33:693-8.
8. Mohan S, Nakao Y, Honda Y, Landale E, Leser U, Dony C,Lang K, Baylink DJ . Studies on the mechanisms by which insulin-like growth factor binding protein (IGFBP-4) and IGFBP-5 modulate IGF actions in bone cells. J Biol Chem. 1995; 270:20424-20431
9. Richman C, Baylink DJ, Lang K, Dony C, Mohan S. Recombinant human insulin-like growth factor binding protein-5 (rhIGFBP-5) stimulates bone formation parameters in vitro and in vivo. Endocrinology.1999; 140:4699-470
10. Miyakoshi N, Richman C, Kasukawa Y, Linkhart TA, Baylink DJB, Mohan S. Evidence that IGF-binding protein-5 functions as a growth factor. J Clin Invest.2001; 107:73-81
11. Conover CA. Regulation and physiological role of insulin-like growth factor binding proteins. Endocr J.1996; 43(Suppl): 43-48
1. Gibson JMC.Multiple injuries:management of the patient with a fractured femur and a head injury.J Bone Joint Surg,1960,42(3):425
2. Spencer RF.The effect of head injury on fracture healing:A quantitative assessment.J Bone Joint Surg,1987.69(4):525
3. Perkins R,Skirving AP.Callus formation and the rate of healing of femoral fractures in patients with head injuries.Journal of Bone and Joint Surgery(British volume), 1987,69:521-524
4. Feeney DM,Boyeson MG,Linn RT,et a1.Responses to cortical injury: Methodology and local effects of contusions in the rat.Brain Res,1981,211:67-77
5. Lighthal JW, Dixon CE, Anderson TE, et al. Experimental models of brain injury. Neurotrauma, 1989, 6:83-97.
6. Gennarelli TA. Mechanisms of brain injury. J Emerg Med, 1993, 11:5.
7. Carbonel l WS, Maris DO, McCall T, et al. Adaptation of the fluid percussion injury model to the mouse. Neurotrauma, 1998, 15:217-229.
8. Sanders MJ, Dietrich WD, Green EJ. Cognitive function following traumatic brain injury: effects of injury severity and recovery period in a parasagittal fluid-percussive injury modeI.J Neurotrauma, 1999, 16: 915-925.
9. DeRoss AL Adams JE, Vane DW, et al. Multiple head injuries in rats:effects on behavior. Trauma.2002, 52:708-714.
10.扬卫红,林敬明,马伯扬,等.大鼠脑冷冻伤引起的脑水肿模型的改进.神经解剖杂志,1999, 15: 299-300
11. Erdincler P,Tuzgen S,Erdincler ED,et al.Influence of aging on hlood-hrain harrier permeability and free radical Formation following experimentalbrain cold injury. Acta Neurochir, 2002, 144:195-199.
12. Nag S. The hIood-hrain harrier and cerebral angiogenesis: Iesions from the cold-injury model. Trends Mol Med, 2002,8:38-49.
13. Garland DE, Rothi B, Waters RL. Femoral fractures in headinjuries adults. Clin Orthop 1982; 219-25.
14.Garland DE, Toder L. Fractures of the tibial diaphysis in adults with head injuries. Clin Orthop 1980; 198-202.
1. Castro RF,Jackson KA,Goodell MA et al.F ailure of bone marrow cells to Transdifferentiate into neural cells in vivo.Science.2002;297:1299
2. Mezey E ,Nagy A ,Szalayova I et al .C omment on“Failure of bone marrow Cells to t ransdiferentiate into neural cell vivo”.Science.2003;299:1184
3. BlauH, BrazeltonT, Keshet G, Rossi F. Something in the eye of the beholder. Science.2002;298:361-362
4. Bobis S, Jarocha D, Majka M. Mesenchymal stem cells: characteristics and clinical applications. Folia Histochem Cytobiol. 2006, 44(4): 215-30
5. Blancor P, Rimiunccib M, Gronthosc S, et al. Bone marrow stromal stem cells:nature, biology and potential applications. Stem Cell, 2001,19(3):180-192
6. Tang Y, Wang R, Zhang C, et al. In vitro differentiation of rat bone mesenchymal stem cells into neuron-like cells induced by vitamin A acid etc. Sichuan Da Xue Xue Bao Yi Xue Ban, 2003, 34:377-80.
7. Frank P, Barrry J, Mary Murphy. Mesenchymal stem cells clinical applications and biological characterization. The International Journal of Biochemistry and Cell Biology.2004,36:568-584
8. Nuttall ME, Patton AJ, et al.Human trabecullar bone cells are able to express both osteoblastic and adipocytic phenotype: implications for osteopenic disorders. J Bone Miner Res, 1998, 13:371-382.
9. Zohar P, Sodek J, McCulloch CA. Characterization of stromal progenitor cells enriched by flow cytometry. Blood. 1997; 90:3471-3481.
10. Herbertson A, Aubin JE. Cell sorting enriches osteogenic populations in rat bone marrow stromal cell cultures. Bone. 1997; 21:491-560.
11. Friedenstein A J, Chailakhyan R K, Gerasimov U V. Bone marrow osteogenic stem cells: in vitro cultivation and transplantation in difusionchambers.Cel Tissue Kinet, 1987,20: 263-72.
12. 1 Pittenger M F, Mackay AM, Beck SC, et al. MuldGneage potential of adult humanmesenchymal stem cells. Science, 1999, 284: 143-147
13. JiangY, JahagirdarBN, Reinhardt RL, et al. Pluripotency of mesenchymal stem cells derived from adult marrow. Nature, 2002, 418 (6893): 41
14. Tocci A, Forte L. Mesenchymal stem cell: use and perspectives. The hematology journal: the official journal of the European Haematology Association / EHA 2003; 4(2):92-6.
15. Kadiyala S, Young RG, Thiede MA, Bruder SP. Culture expanded canine mesenchymal stem cells possess osteochondrogenic potential in vivo and in vitro. Cell transplantation 1997; 6(2):125-34.
16. Friedenstein AJ. Precursor cells of mechanocytes. International review of cytology 1976; 47:327-59.
17. Nagatomo K, Komaki M, Sekiya I, Sakaguchi Y, Noguchi K, Oda S. Stem cell properties of human periodontal ligament cells. Journal of periodontal research 2006; 41(4):303-10.
18. Lorenz MR, Holzapfel V, Musyanovych A, Nothelfer K, Walther P, Frank H. Uptake of functionalized, fluorescent-labeled polymeric particles in different cell lines and stem cells. Biomaterials 2006; 27(14):2820-8.
19. Kotobuki N, Hirose M, Machida H, Katou Y, Muraki K, Takakura Y. Viability and osteogenic potential of cryopreserved human bone marrow-derived mesenchymal cells. Tissue engineering 2005; 11(5-6):663-73.
20. Fukuchi Y, Nakajima H, Sugiyama D, Hirose I, Kitamura T, Tsuji K. Human placenta-derived cells have mesenchymal stem/progenitor cell potential. Stem cells, 2004; 22(5):649-58.
21. Fortier LA, Nixon AJ, Williams J. Isolation and chondrocytic differentiation of equine bone marrow derived mesenchymal stem cells. Am J Vet Res, 1998, 59:1182-1187.
22.司徒镇强,吴军正,单立冬,杨天明等.差速贴壁法分离培养早期人胚胎骨髓间充质干细胞.东南大学学报,2005,24(4):218-221.
23 Pitienger MF, Mackay AM, Beck SC, et al. Multilineage potential of adult human mesenchymal stem cells. Science.1999,284(5411):143-147。
1. Feeney DM,Boyeson MG,Linn RT,et a1.Responses to cortical injury:I Methodology and local effects of contusions in the rat.Brain Res,1981,21 1:67-7
2. Perkins R,Skirving AP.Callus formation and the rate of healing of femoral fractures in patients with head injuries.Journal of Bone and Joint Surgery(British volume) 1987;69:521-52
3. Markowitz NR, Cranial bone grafting in oral and maxillofacial surgery J Am Dent Assoc, Jul 1992; 123: 206-211.
4. Zins JE, Whitaker LA, Membranous versus endochondral bone:implications for craniofacial reconstruction. Plast Reconstr Surg,1983,72:778.
5. Kusak JF,Zins JE.Whitaker LA. The early revascularization of membranous bone. Plast Reconstr Surg,1985,76:510
6. Donovan MG,Dickerson NC,Hellstein JW, et al. Autologous calvarial and ilac onlay bone grafts in miniature swine. J Oral Maxillofac Surg 1993.51:898
7. Celik MR.A simple method for cranial bone chip harvesting.Ann Plast-Surg,2003,51(4):434-435
8. Fearen JA.AMagneticResonanceImesing Investigation of Potential Subolinieal Complications after in Situ Cranial Bone Graft Han'est.Plastic&BeconstructiveSurgery,200O,105(6):1935-1939
9. Melega JM.Cranial Bone Graft for the Maxillary Sinus Floor.Plastic and Reconstructive Surgery,2003.111(2):972
1. Mohan S, Nakao Y, Honda Y, Landale E, Leser U, Dony C,Lang K, Baylink DJ (1995) Studies on the mechanisms by which insulin-like growth factor binding protein (IGFBP-4) and IGFBP-5 modulate IGF actions in bone cells. J Biol Chem 270:20424–20431
2. Richman C, Baylink DJ, Lang K, Dony C, Mohan S. Recombinant human insulin-like growth factor binding protein-5 (rhIGFBP-5) stimulates bone formation parameters in vitro and in vivo. Endocrinology.1999.140:4699–470
3. Miyakoshi N, Richman C, Kasukawa Y, Linkhart TA, Baylink DJB, Mohan S. Evidence that IGF-binding protein-5 functions as a growth factor. J Clin Invest 2001.107:73–81
4. Conover CA. Regulation and physiological role of insulin-like growth factor binding proteins. Endocr J.1996.43 (Suppl): 43-48
5. Feeney DM,Boyeson MG,Linn RT,et a1.Responses to cortical injury:I Methodology and local effects of contusions in the rat.Brain Res,1981,21:67-77
1. Gibson JMC.Multiple injuries:management of the patient with a fracturedfemur and a head injury.J Bone Joint Surg(Sr),1960,42(3):425
2. Bidner SM, Rubins IM, Desjardins JV, Zukor DJ, Goltzman D. Evidence for a humoral mechanism for enhanced osteogenesis after head injury. J Bone Joint Surg Am 1990; 72:1144-9.
3. Newman RJ, Stone MH, Mukherjee SK. Accelerated fracture union in association with severe head injury. Injury 1987;18:241
4. Perkins R, Skirving AP. Callus formation and the rate of healing of femoral fractures in patients with head injuries. J Bone Joint Surg Br 1987; 69:521-4.
5. Roberts Heterotopic ossification complicating paralysis of intracranial origin. J Bone Joint Surg Br 1968;50-B:70-7.
6. Citta-Pietrolungo TJ, Alexander MA, Steg NL. Early detection of heterotopic ossification in young patients with traumatic brain injury. Arch Phys Med Rehabil 1992; 73:258-62.
7. Smith R. Head injury, fracture healing and callus. J Bone Joint Surg Br 1987; 69:518—20.
8. Spencer RF. The effect of head injury on fracture healing. A quantitative assessment. J Bone Joint Surg Br 1987; 69:525-8.
9. Boulet M, Marier JR. Precipitation of calcium phosphates from solution at near physiological concentration. Arch Biochem 1961; 93:157.
10. Wildburger R,Zarkovic N,Tonkovic G,et a1.Post- traumatic hormonal disturbances:pmlactin as a link between head injury and enhanced osteogenesis.J Endocrinol Invest,1998,21(1):78
11. Khare GN,Gautam VK,Gupta LN ,el a1.A new hypothesis for faster healing of fractures in hem injured patients.Indian J Med Sci,1995,49(2):281
12. Dewulf N,Verschuren K,Lonnoy O,Moren A,et a1. Distinct spatial and temporal expression patterns of two type I receptors for bone morphogenic proteins during mouse embryiogenesis.Endoerinology,1995,136(12):2652
13. Scherbel U,Riess P,Khurana JS,et a1.Expression of Bone Marphogenic Proteins in Rats with and without Brain lnjnry and a Tibia Fracture.The University of Pennsylvania Orthopaedic Journa1.2001,14(1):85
14. Yaoita H,Orimo H,Shirai Y. Shimada T. Expression of bone morphogenic proteins less homolog genes following rat femoral fracture.J Bone Miuer Metab 2000,18(1):63
15. Walter HJ,Berry M,Hill DJ,et a1.Sptial and temporal changes in the insulin-like growth factor(1GF)axis indicate autoefine/paracfine action ofIGF-1 within wounds ofthe brain.Endocrinology. 1997,138(7):3024
16. Beeton CA,Brooks RA,Rushton N.Circulating levels of insulin- like growth factor
1 and insulin-like growth factor binding protein-3 in patients with severe head injury.J Bone Joint Surg(Br),2002,84(3):434
17. Brinker MR, Miller MD. Basic sciences: bone injury and repair. In: Miller M, editor. Review of Orthopaedics. 3rd ed. Saunders WB; 2000. p. 19-22.
18. Wildburger R, Zarkovic N, Egger G, PetekW, Zarkovic K, Hofer HP. Basic fibroblast growth factor (BFGF) immunoreactivity as a possible link between head injury and impaired bone fracture healing. Bone Miner 1994; 27:183-92.
19. Wildburger R, Zarkovic N, Egger G, et al. Comparison of the values of basic fibroblast growth factor determined by an immunoassay in the sera of patients with traumatic brain injury and enhanced osteogenesis and the effects of the same sera on the fibroblast growth in vitro. Eur J Clin Chem Clin Biochem 1995; 33:693-8.
20.汪学军,裴福兴,池雷霆,等.骨折合并脑外伤时骨愈合过程中bFGF作用的实验研究.中华骨科杂志,2003,23(1):5
21. Malcangio M,Garrett NE,Tomlinson DR.Nerve growth factor treatment increases stimulus-evoked re]ease of sensory neuropep-tides in the rat Spinal Cord.Eur JNeurosci,1997,9(6):101
22. Grills BL.Schuijers JA,Ward AR.Topical application of new growth factor improves fracture healing in rats.J Orthop Res,1997.15(3):235
23. Madsen JE. Hukkanen M.Aune AK.et 81.Fraetune healing and callus innervation after peripheral nerve resection in rats.Clin Orthop.1998,351(2):230
24. Konttinen Y'F,Imai S,Suda A.Neuropeptides an d the puzzle of bone remodeling.Acta Ohop Scand,1996. 67(4):63
25. Shih C,Bernard GW .Neurogenie substance P stimulates osteoganesis in vitro.Peptides,1997. 18(3):323
26. Rameshwar P,Gascon P.Substance P(SP)mediates production of stem cell factor and interleukin-1 in bone mTOW strnma:Potential autoregulatory role for these cytokines in SP receptor expression and induction.Blood,1995.86(3):482
27. Vignery A.McCarthy. The neuropeptide calcitonin gene-related peptlde stimulates insulin—like growth factor I production by primary fetal rat ostooblasts.Bone,1996,18(2):33
28. Garland DE, Rothi B, Waters RL. Femoral fractures in headinjuries adults. Clin Orthop 1982;219-25.
29. Garland DE, Toder L. Fractures of the tibial diaphysis in adults with head injuries. Clin Orthop 1980; 198-202.
30. Garland DE, Dowling V. Forearm fractures in the head-injured adult. Clin Orthop 1983; 176:190-6.
31. Kushwaha VP, Garland DG. Extremity fractures in the patient with a traumatic brain injury. J Am Acad Orthop Surg 1998; 6:298-307.
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