The role of JAK1/2 kinases in the development of neurogenic heterotopic ossification following spinal cord injury
Neurogenic heterotopic ossification is a complex disease that is characterized by the formation of heterotopic bone in soft tissues following central nervous system injuries and various neurological disorders. The exact mechanism of the disease and the factors that play a role in its development are still unknown and they comprise a promising research field. However, understanding the pathophysiology of the disease can lead us to diagnosis and help us find more effective ways of treatment.
The JAK-STAT signaling pathway is a mechanism of cellular signaling that is involved in many processes of the organism, such as the development of the skeletal system and the regulation of the neuroinflammatory response that follows spinal cord injuries. The purpose of this study is the research of the bibliography concerning the role of these JAK1 and JAK2 tyrosine-kinases in the development of neurogenic heterotopic ossification following spinal cord injuries.
D. Shehab, A. H. Elgazzar, and B. D. Collier, “Heterotopic ossification.,” J. Nucl. Med. 2002;43:345-53, [Online]. Available: http://www.ncbi.nlm.nih.gov/pubmed/11884494.
Subbarao JV, Garrison SJ. “Heterotopic ossification: Diagnosis and management, current concepts and controversies,” J. Spinal Cord Med .1999;22:273–283
Nauth A et al., “Heterotopic ossification in orthopaedic trauma.,” J. Orthop. Trauma 2012;26:684-8, doi: 10.1097/BOT.0b013e3182724624.
Reichel LM, Salisbury E, Moustoukas MJ, DavisAR, Olmsted-Davis E, “Molecular Mechanisms of Heterotopic Ossification,” J. Hand Surg. Am.,2014;39:563-566, doi: 10.1016/j.jhsa.2013.09.029.
Pape CH, MarshS, Morley JR, Krettek C, Giannoudis PV, “Current concepts in the development of heterotopic ossification,” J. Bone Joint Surg. Br., 2004;86-B:783–787, doi: 10.1302/0301-620X.86B6.15356.
Vanden Bossche L, Vanderstraeten G. “Heterotopic ossification: A review,” J. Rehabil. Med. 2005;37:129–136, doi: 10.1080/16501970510027628.
Zychowicz ME. “Pathophysiology of heterotopic ossification.,” Orthop. Nurs., 2013;32:173–7, doi: 10.1097/NOR.0b013e3182920d85.
McCarthy EF, Sundaram M. “Heterotopic ossification: a review,” Skeletal Radiol. 2005;34:609–619, doi: 10.1007/s00256-005-0958-z.
Meyers Cet al. “Heterotopic Ossification: A Comprehensive Review,” JBMR Plus, 2019;3:e10172, doi: 10.1002/jbm4.10172.
Hinck S., “Heterotopic Ossification: A Review of Symptoms and Treatment,” Rehabil. Nurs. 1994;19:169–173, doi: 10.1002/j.2048-7940.1994.tb01578.x.
da Paz AC, Carod Artal FJ, Kalil RK. “The function of proprioceptors in bone organization: A possible explanation for neurogenic heterotopic ossification in patients with neurological damage,” Med. Hypotheses 2007;68:67–73, doi: 10.1016/j.mehy.2006.06.035.
Seipel R, Langner S, Platz T, Lippa M, Kuehn JP, Hosten N. “Neurogenic heterotopic ossification: epidemiology and morphology on conventional radiographs in an early neurological rehabilitation population,” Skeletal Radiol. 2012;41:61–66, doi: 10.1007/s00256-011-1115-5.
Sakellariou VI, Grigoriou E, Mavrogenis AF, Soucacos PN, Papagelopoulos PJ. “Heterotopic ossification following traumatic brain injury and spinal cord injury: insight into the etiology and pathophysiology” J. Musculoskelet. Neuronal Interact., 2012;12:230–40, Available: http://www.ncbi.nlm.nih.gov/pubmed/23196266.
Mavrogenis AF, Guerra G, Staals EL, Bianchi G, Ruggieri P. “A classification method for neurogenic heterotopic ossification of the hip,” J. Orthop. Traumatol., 2012;13:69–78, doi: 10.1007/s10195-012-0193-z.
Van Kuijk AA. Geurts ACH, Van Kuppevelt HJM. “Neurogenic heterotopic ossification in spinal cord injury,” Spinal Cord. 2002;40:313–326, doi: 10.1038/sj.sc.3101309.
Sullivan MP, Torres SJ, Mehta S,. Ahn J. “Heterotopic ossification after central nervous system trauma,” Bone Joint Res. 2013;2:51–57, doi: 10.1302/2046-3758.23.2000152.
Brady RD, Shultz SR, McDonald SJ, O’Brien TJ. “Neurological heterotopic ossification: Current understanding and future directions” Bone 2018;109:35–42, doi: 10.1016/j.bone.2017.05.015.
Genêt F et al., “Neurological heterotopic ossification following spinal cord injury is triggered by macrophage-mediated inflammation in muscle,” J. Pathol. 2015;236:229–240, doi: 10.1002/path.4519.
Reznik JE et al., “Prevalence and risk-factors of neurogenic heterotopic ossification in traumatic spinal cord and traumatic brain injured patients admitted to specialised units in Australia.,” J. Musculoskelet. Neuronal Interact.,2014;14:19–28, [Online]. Available: http://www.ncbi.nlm.nih.gov/pubmed/24583537.
Edwards DS, Clasper JC. “Heterotopic ossification: a systematic review,” J. R. Army Med. Corps, 2015;161:315–321, doi: 10.1136/jramc-2014-000277.
Zeckey C, Hildebrand F, Frink M, Krettek C. “Heterotopic ossifications following implant surgery--epidemiology, therapeutical approaches and current concepts.,” Semin. Immunopathol., 2011;33:273–86, doi: 10.1007/s00281-011-0240-5.
Ranganathan K et al., “Heterotopic Ossification,” J. Bone Jt. Surg. 2015;97:1101–1111, doi: 10.2106/JBJS.N.01056.
Debaud C et al., “Peripheral denervation participates in heterotopic ossification in a spinal cord injury model,” PLoS One, 2017;12:e0182454, doi: 10.1371/journal.pone.0182454.
Zhao Y et al. “Development process of traumatic heterotopic ossification of the temporomandibular joint in mice,” J. Cranio-Maxillofacial Surg. 2019;47:1155–1161, doi: 10.1016/j.jcms.2018.11.026.
Tuzmen C, Verdelis K, Weiss L, Campbell P. “Crosstalk between substance P and calcitonin gene-related peptide during heterotopic ossification in murine Achilles tendon,” J. Orthop. Res., 2018;36:1444–1455, doi: 10.1002/jor.23833.
Davis EL,. Davis AR, Gugala Z Olmsted-Davis EA. “Is heterotopic ossification getting nervous?: The role of the peripheral nervous system in heterotopic ossification,” Bone, 2018;109:22–27, doi: 10.1016/j.bone.2017.07.016.
Ramirez DM, Ramirez RM,. Reginato AM, Medici D. “Molecular and cellular mechanisms of heterotopic ossification.,” Histol. Histopathol., 2014;29:1281–5, doi: 10.14670/HH-29.1281.
Łęgosz P, Drela K, Pulik L, Sarzyńsk S, Małdyk P, “Challenges of heterotopic ossification—Molecular background and current treatment strategies,” Clin. Exp. Pharmacol. Physiol., 2018;45:1229–1235, doi: 10.1111/1440-1681.13025.
Xiao Q, Du Y, Wu W, Yip HK, “Bone morphogenetic proteins mediate cellular response and, together with Noggin, regulate astrocyte differentiation after spinal cord injury,” Exp. Neurol., 2010;221:353–366, doi: 10.1016/j.expneurol.2009.12.003.
Gensel JC, Zhang CB. “Macrophage activation and its role in repair and pathology after spinal cord injury,” Brain Res. 2015;1619:1–11, doi: 10.1016/j.brainres.2014.12.045.
Dai J et al. “MicroRNA-125b promotes the regeneration and repair of spinal cord injury through regulation of JAK/STAT pathway,” Eur. Rev. Med. Pharmacol. Sci 2018;22:582–589, doi: 10.26355/eurrev_201802_14271.
Dai J et al., “MicroRNA-210 promotes spinal cord injury recovery by inhibiting inflammation via the JAK-STAT pathway,” Eur. Rev. Med. Pharmacol. Sci.,2018;22:6609–6615, doi: 10.26355/eurrev_201810_16135.
Ahn YH, Bae Yeon Y, Lee G, Kang Mee K, Kang SK. “Molecular insights of the injured lesions of rat spinal cords: Inflammation, apoptosis, and cell survival,” Biochem. Biophys. Res. Commun., 2006; 348:560–570, doi: 10.1016/j.bbrc.2006.07.105.
Yan Z, Gibson SA, Buckley JA, Qin H, Benveniste NE, “Role of the JAK/STAT signaling pathway in regulation of innate immunity in neuroinflammatory diseases.,” Clin. Immunol., 2018;189:4–13, doi: 10.1016/j.clim.2016.09.014.
Yamauchi K et al., “Activation of JAK/STAT signalling in neurons following spinal cord injury in mice,” J. Neurochem., 2006;96:1060–1070, doi: 10.1111/j.1471-4159.2005.03559.x.
Moresi V, Adamo S, Berghella L. “The JAK/STAT Pathway in Skeletal Muscle Pathophysiology,” Front. Physiol., 2019;10:1–10, doi: 10.3389/fphys.2019.00500.
Roskoski R, “Janus kinase (JAK) inhibitors in the treatment of inflammatory and neoplastic diseases,” Pharmacol. Res., 2016;111:784–803, doi: 10.1016/j.phrs.2016.07.038.
Levy JB, “Activation of the JAK-STAT signal transduction pathway by oncostatin-M cultured human and mouse osteoblastic cells,” Endocrinology, 1996;137:1159–1165, doi: 10.1210/en.137.4.1159.
Wang T et al., “The role of the JAK-STAT pathway in neural stem cells, neural progenitor cells and reactive astrocytes after spinal cord injury,” Biomed. Reports, 2015;3:141–146, doi: 10.3892/br.2014.401.
Li J. JAK-STAT and bone metabolism. JAK-STAT, 2013;2:e23930, doi: 10.4161/jkst.23930.
Gotthardt D, Trifinopoulos J, Sexl V, Putz EM, “JAK/STAT Cytokine Signaling at the Crossroad of NK Cell Development and Maturation,” Front. Immunol., 2019;10:1–16, doi: 10.3389/fimmu.2019.02590.
Park KW, Lin CY, Benveniste EN, Lee YS. “Mitochondrial STAT3 is negatively regulated by SOCS3 and upregulated after spinal cord injury.,” Exp. Neurol., 2016;284:98–105, doi: 10.1016/j.expneurol.2016.08.002.
Tapia VS, Herrera-Rojas M, Larrain J. “JAK-STAT pathway activation in response to spinal cord injury in regenerative and non-regenerative stages of Xenopus laevis,” Regeneration, 2017;4:21–35, doi: 10.1002/reg2.74.
Hudson SJ, Brett SJ. “Heterotopic ossification--a long-term consequence of prolonged immobility.,” Crit. Care, 2006;10:174, doi: 10.1186/cc5091.
Zhang X et al., “SOCS3 Attenuates GM-CSF/IFN-γ-Mediated Inflammation During Spontaneous Spinal Cord Regeneration,” Neurosci. Bull.,2020;36:778–792, doi: 10.1007/s12264-020-00493-8.
Ning SL, Zhu H, Shao J, Liu YC, Lan J, Mia J., “MiR-21 inhibitor improves locomotor function recovery by inhibiting IL-6R/JAK-STAT pathway-mediated inflammation after spinal cord injury in model of rat,” Eur. Rev. Med. Pharmacol. Sci.,2019;23:433–440, doi: 10.26355/eurrev_201901_16852.
Alexander KA et al., “Inhibition of JAK1/2 Tyrosine Kinases Reduces Neurogenic Heterotopic Ossification After Spinal Cord Injury.,” Front. Immunol., 2019;10:377, doi: 10.3389/fimmu.2019.00377.
H. Tseng et al., “Neurogenic heterotopic ossifications develop independently of granulocyte‐colony stimulating factor and neutrophils,” J. Bone Miner. Res., p. jbmr.4118, Jun. 2020, doi: 10.1002/jbmr.4118.
Li JW, Kuang Y, Chen YL, Wang JF. “LncRNA ZNF667-AS1 inhibits inflammatory response and promotes recovery of spinal cord injury via suppressing JAK-STAT pathway,” Eur. Rev. Med. Pharmacol. Sci., 2018;22:7614–7620, doi: 10.26355/eurrev-201811-16375.
El Jammal T, Gerfaud-Valentin M, Sève P, Jamilloux Y. “Inhibition of JAK/STAT signaling in rheumatologic disorders: The expanding spectrum,” Jt. Bone Spine, 2020;87:119–129, doi: 10.1016/j.jbspin.2019.09.005.
Cui M, Ma X, Sun J, He J, Shen L, Li F. “Effects of STAT3 inhibitors on neural functional recovery after spinal cord injury in rats,” Biosci. Trends,2016;10:460–466, doi: 10.5582/bst.2016.01160.
Salisbury E, Sonnet C, Heggeness M, Davis AR, and E. Olmsted-Davis E. “Heterotopic ossification has some nerve.,” Crit. Rev. Eukaryot. Gene Expr.,2010;20:313–24, doi: 10.1615/critreveukargeneexpr.v20.i4.30.
Dong L, Dong G, Cao J, Zhang J. “Association of α2-HS Glycoprotein with Neurogenic Heterotopic Ossification in Patients with Spinal Cord Injury,” Med. Sci. Monit., 2017;23:5382-5388, doi: 10.12659/MSM.904626.
Torossian F et al., “Macrophage-derived oncostatin M contributes to human and mouse neurogenic heterotopic ossifications,” JCI Insight, 2017;2:21,Cdoi: 10.1172/jci.insight.96034.
Tirone M et al., “Severe Heterotopic Ossification in the Skeletal Muscle and Endothelial Cells Recruitment to Chondrogenesis Are Enhanced by Monocyte/Macrophage Depletion,” Front. Immunol., 2019;10:1640,, doi: 10.3389/fimmu.2019.01640.
Zhang X et al., “Oncostatin M receptor β deficiency attenuates atherogenesis by inhibiting JAK2/STAT3 signaling in macrophages,” J. Lipid Res.,2017;58:895–906, doi: 10.1194/jlr.M074112.
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