创伤性异位骨化相关调控因子及信号通路研究进展

摘要/Abstract

摘要： 创伤性异位骨化（THO）常发生于外伤或手术后,表现为在软组织中形成异位的骨组织，是临床中较为常见的现象和并发症。THO的发生是多种因素共同作用的结果，本文就THO发生的分子机制相关研究进展进行综述。

关键词: 创伤性异位骨化, 转化生长因子-β, 骨形态发生蛋白, 刺猬蛋白, Wnt 信号通路

Abstract: Traumatic heterotopic ossification (THO) is characterized by the formation of bone tissue in soft tissue after trauma or operation, which is a common clinical phenomenon and complication. THO is the result of the joint efforts of many factors, and the progress of molecular mechanism in THO was systematically reviewed in this article.

Key words: Traumatic heterotopic ossification, Transforming growth factor β, BMP, Hedgehog, Wnt signaling pathway

朱悦顾佳颖代杰文. 创伤性异位骨化相关调控因子及信号通路研究进展[J]. 口腔生物医学, 2021, 12(4): 262-266.

参考文献 53

[1]	Ranganathan K, Loder S, Agarwal S, et al. Heterotopic Ossification: Basic-Science Principles and Clinical Correlates[J]. Journal of Bone & Joint Surgery-american Volume, 2015, 97(13):1101-1111.
[2]	Casavant AM, Hill Hastings II. Heterotopic Ossification about the Elbow: A Therapist's Guide to Evaluation and Management[J]. Journal of Hand Therapy, 2006, 19(2):255-267.
[3]	Schwarzkopf R, Cohn RM, Skoda EC, et al. The predictive power of preoperative hip range of motion for the development of heterotopic ossification[J]. Orthopedics, 2011, 34(3):169.
[4]	Foster N, Kornhaber R, McGarry S, et al. Heterotopic Ossification in adults following a burn: A phenomenological analysis[J]. Burns,2017, 43(6):1250-1262.
[5]	Linan E , O’Dell, Michael W, et al. Continuous passive motion in the management of heterotopic ossification in a brain injured patient[J]. American Journal of Physical Medicine & Rehabilitation, 2001, 80(8):614-617.
[6]	Foley KL, Hebela N, Keenan MA, et al. Histopathology of periarticular non-hereditary heterotopic ossification[J]. Bone,2018,109:65-70.
[7]	Zhao Y, Liu P, Chen Q, et al. Development process of traumatic heterotopic ossification of the temporomandibular joint in mice[J]. J Craniomaxillofac Surg,2019,47(7):1155-1161.
[8]	Wang X, Li F, Xie L, et al. Inhibition of overactive TGF-β attenuates progression of heterotopic ossification in mice[J]. Nat Commun,2018,9(1):551.
[9]	Mao D, Pan X, Rui Y, et al. Matrine attenuates heterotopic ossification by suppressing TGF-β induced mesenchymal stromal cell migration and osteogenic differentiation[J]. Biomed Pharmacother,2020,127:110152.
[10]	Sorkin M, Huber AK, Hwang C, et al. Regulation of heterotopic ossification by monocytes in a mouse model of aberrant wound healing[J]. Nat Commun,2020,11(1):722.
[11]	Li L, Tuan RS. Mechanism of traumatic heterotopic ossification: In search of injury-induced osteogenic factors[J]. J Cell Mol Med,2020,24(19):11046-11055.
[12]	Xu J, Liu J, Gan Y, et al. High-Dose TGF-β1 Impairs Mesenchymal Stem Cell-Mediated Bone Regeneration via Bmp2 Inhibition[J]. J Bone Miner Res, 2020,35(1):167-180.
[13]	Deschaseaux F, Sensébé L, Heymann D. Mechanisms of bone repair and regeneration[J]. Trends Mol Med,2009,15(9):417‐429.
[14]	Yu PB, Deng DY, Lai CS, et al. Erratum: BMP type I receptor inhibition reduces heterotopic ossification[J]. Nat Med,2008,14(12):1363-9.
[15]	Sun DM, Liu ZB, Zhao Y, et al. Runx2 is involved in regulating osterix promoter activity and gene expression[J].Sheng wu hua xue yu Sheng wu wu li jin Zhan,2006,33(10):957-964.
[16]	Agarwal S, Loder SJ, Breuler C, et al. Strategic Targeting of Multiple BMP Receptors Prevents Trauma-Induced Heterotopic Ossification[J]. Molecular Therapy the Journal of the American Society of Gene Therapy,2017,25(8):1974-1987.
[17]	Evans KN, Potter BK, Brown TS, et al. Osteogenic gene expression correlates with development of heterotopic ossification in war wounds[J]. Clin Orthop Relat Res,2014,472(2):396-404.
[18]	Peterson JR, De La Rosa S, Eboda O, et al. Treatment of heterotopic ossification through remote ATP hydrolysis[J]. Sci Transl Med,2014,6(255):255ra132.
[19]	Kan L, Kessler JA . Animal Models of Typical Heterotopic Ossification[J]. Journal of Biomedicine and Biotechnology,2011, 2011(263):309287.
[20]	Hashimoto K, Kaito T, Furuya M. et al. In vivo dynamic analysis of BMP-2-induced ectopic bone formation[J]. Sci Rep,2020,10(1):4751.
[21]	Kan L, Hu M, Gomes WA, et al. Transgenic mice overexpressing BMP4 develop a fibrodysplasia ossificans progressiva (FOP)-like phenotype[J]. Am J Pathol,2004,165(4):1107-1115.
[22]	Yan YB, Li JM, Xiao E, et al. A pilot trial on the molecular pathophysiology of traumatic temporomandibular joint bony ankylosis in a sheep model. Part II: The differential gene expression among fibrous ankylosis, bony ankylosis and condylar fracture[J]. J Craniomaxillofac Surg,2014,42(2):e23‐e28.
[23]	Chen, D., Harris, M., Rossini, G. et al. Bone Morphogenetic Protein 2 (BMP-2) Enhances BMP-3, BMP-4, and Bone Cell Differentiation Marker Gene Expression During the Induction of Mineralized Bone Matrix Formation in Culturesof Fetal Rat Calvarial Osteoblasts[J]. Calcif Tissue Int,1997,60(3):283-90.
[24]	Li L , Jiang Y , Lin H , et al. Muscle injury promotes heterotopic ossification by stimulating local bone morphogenetic protein-7 production[J]. Journal of Orthopaedic Translation,2019,18:142-153.
[25]	Leblanc E , Frédéric Trensz, Haroun S , et al. BMP-9-induced muscle heterotopic ossification requires changes to the skeletal muscle microenvironment[J]. Journal of Bone & Mineral Research, 2011, 26(6):1166-1177.
[26]	Kim JM, Yang YS, Park KH, et al. A RUNX2 stabilization pathway mediates physiologic and pathologic bone formation[J]. Nat Commun,2020,11(1):2289.
[27]	Kan L, Lounev VY, Pignolo RJ, et al. Substance P signaling mediates BMP-dependent heterotopic ossification[J]. J Cell Biochem,2011,112(10):2759-72.
[28]	Alman BA. The role of hedgehog signalling in skeletal health and disease[J].Nat Rev Rheumatol,2015,11(9):552-60.
[29]	Briscoe J, Thérond PP. The mechanisms of Hedgehog signalling and its roles in development and disease[J]. Nat Rev Mol Cell Biol,2013,14(7):416-429.
[30]	Kan C, Chen L, Hu Y, et al. Gli1-labeled adult mesenchymal stem/progenitor cells and hedgehog signaling contribute to endochondral heterotopic ossification[J]. Bone, 2018,109:71-79.
[31]	Kan C , Ding N , Yang J , et al. BMP-dependent, injury-induced stem cell niche as a mechanism of heterotopic ossification[J]. Stem Cell Research & Therapy, 2019,10(1):14.
[32]	Zhang D, Schwarz EM, Rosier RN, et al. ALK2 functions as a BMP type I receptor and induces Indian hedgehog in chondrocytes during skeletal development[J]. J Bone Miner Res, 2003,18(9):1593-604.
[33]	Minina E, Wenzel HM, Kreschel C, et al. BMP and Ihh/PTHrP signaling interact to coordinate chondrocyte proliferation and differentiation[J]. Development,2001,128(22):4523-34.
[34]	Clevers H, Nusse R. Wnt/β-catenin signaling and disease[J]. Cell,2012,149(6):1192-205.
[35]	Zhao Y, Ouyang N, Chen L, et al. Stimulating Factors and Origins of Precursor Cells in Traumatic Heterotopic Ossification Around the Temporomandibular Joint in Mice[J]. Front Cell Dev Biol,2020,8:445.
[36]	Komori T. Roles of Runx2 in Skeletal Development[J]. Adv Exp Med Biol,2017,962:83-93.
[37]	Tu B, Liu S, Yu B, et al. miR-203 inhibits the traumatic heterotopic ossification by targeting Runx2[J]. Cell Death Dis,2016,7(10):e2436.
[38]	Feng L, Zhang JF, Shi L, et al. MicroRNA-378 Suppressed Osteogenesis of MSCs and Impaired Bone Formation via Inactivating Wnt/β-Catenin Signaling[J]. Mol Ther Nucleic Acids,2020,21:1017-1028.
[39]	Yang B, Li S, Chen Z, et al. Amyloid β peptide promotes bone formation by regulating Wnt/β-catenin signaling and the OPG/RANKL/RANK system[J]. FASEB J,2020,34(3):3583-3593.
[40]	Qu F, Wang J, Xu N, et al. WNT3A modulates chondrogenesis via canonical and non-canonical Wnt pathways in MSCs[J]. Front Biosci (Landmark Ed),2013,18:493-503.
[41]	Kan C, Chen L, Hu Y, et al. Conserved signaling pathways underlying heterotopic ossification[J]. Bone,2018,109:43-48.
[42]	Weston AD, Chandraratna RA, Torchia J, et al. Requirement for RAR-mediated gene repression in skeletal progenitor differentiation[J]. J Cell Biol,2002,158(1):39-51.
[43]	Chakkalakal SA, Uchibe K, Convente MR, et al. Palovarotene Inhibits Heterotopic Ossification and Maintains Limb Mobility and Growth in Mice With the Human ACVR1(R206H) Fibrodysplasia Ossificans Progressiva (FOP) Mutation[J]. J Bone Miner Res,2016,31(9):1666-75.
[44]	Shimono K, Tung WE, Macolino C, et al. Potent inhibition of heterotopic ossification by nuclear retinoic acid receptor-γ agonists[J]. Nat Med,2011,17(4):454-60.
[45]	Rajicic N, Cuschieri J, Finkelstein DM, et al. Identification and interpretation of longitudinal gene expression changes in trauma[J]. PLoS One,2010,5(12):e14380.
[46]	Agarwal S, Loder S, Brownley C, et al. Inhibition of Hif1α prevents both trauma-induced and genetic heterotopic ossification[J]. Proc Natl Acad Sci U S A,2016,113(3):E338-E347.
[47]	Lin L, Shen Q, Leng H, et al. Synergistic inhibition of endochondral bone formation by silencing Hif1α and Runx2 in trauma-induced heterotopic ossification[J]. Mol Ther,2011,19(8):1426-1432.
[48]	Huang YF, Wang XY, Lin H. The hypoxic microenvironment: a driving force for heterotopic ossification progression[J]. Cell communication and signaling : CCS,2020,18(1):20.
[49]	Zhang Q, Zhang Y, Yan M, et al. βig-h3 enhances chondrogenesis via promoting mesenchymal condensation in rat Achilles tendon heterotopic ossification model[J]. Aging (Albany NY),2020,12(8):7030-7041.
[50]	Zhang J, Wang L, Chu J, et al. Macrophage-derived neurotrophin-3 promotes heterotopic ossification in rats[J]. Lab Invest,2020,100(5):762-776.
[51]	Su YW, Chim SM, Zhou L, et al. Osteoblast derived-neurotrophin?3 induces cartilage removal proteases and osteoclast-mediated function at injured growth plate in rats[J]. Bone,2018,116:232-247.
[52]	Zhang J, Wang L, Cao H, et al. Neurotrophin-3 acts on the endothelial-mesenchymal transition of heterotopic ossification in rats[J]. J Cell Mol Med,2019,23(4):2595-2609.
[53]	Yuasa M, Mignemi NA, Nyman JS, et al. Fibrinolysis is essential for fracture repair and prevention of heterotopic ossification[J]. J Clin Invest,2015,125(8):3117-31.