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Pathophysiology and Emerging Molecular Therapeutic Targets in Heterotopic Ossification

1
Department of Oncology and Metabolism, The Medical School, University of Sheffield, Beech Hill Road, Sheffield S10 2RX, UK
2
Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield S10 2RX, UK
*
Author to whom correspondence should be addressed.
Academic Editor: José Manuel López
Int. J. Mol. Sci. 2022, 23(13), 6983; https://doi.org/10.3390/ijms23136983
Received: 26 May 2022 / Revised: 19 June 2022 / Accepted: 22 June 2022 / Published: 23 June 2022
(This article belongs to the Special Issue Bone Development and Growth)
The term heterotopic ossification (HO) describes bone formation in tissues where bone is normally not present. Musculoskeletal trauma induces signalling events that in turn trigger cells, probably of mesenchymal origin, to differentiate into bone. The aetiology of HO includes extremely rare but severe, generalised and fatal monogenic forms of the disease; and as a common complex disorder in response to musculoskeletal, neurological or burn trauma. The resulting bone forms through a combination of endochondral and intramembranous ossification, depending on the aetiology, initiating stimulus and affected tissue. Given the heterogeneity of the disease, many cell types and biological pathways have been studied in efforts to find effective therapeutic strategies for the disorder. Cells of mesenchymal, haematopoietic and neuroectodermal lineages have all been implicated in the pathogenesis of HO, and the emerging dominant signalling pathways are thought to occur through the bone morphogenetic proteins (BMP), mammalian target of rapamycin (mTOR), and retinoic acid receptor pathways. Increased understanding of these disease mechanisms has resulted in the emergence of several novel investigational therapeutic avenues, including palovarotene and other retinoic acid receptor agonists and activin A inhibitors that target both canonical and non-canonical signalling downstream of the BMP type 1 receptor. In this article we aim to illustrate the key cellular and molecular mechanisms involved in the pathogenesis of HO and outline recent advances in emerging molecular therapies to treat and prevent HO that have had early success in the monogenic disease and are currently being explored in the common complex forms of HO. View Full-Text
Keywords: heterotopic ossification; genetics; bone morphogenetic protein; activin A/ALK2; retinoic acid receptor; Hoxa11+ mesenchymal stromal cells heterotopic ossification; genetics; bone morphogenetic protein; activin A/ALK2; retinoic acid receptor; Hoxa11+ mesenchymal stromal cells
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MDPI and ACS Style

Felix-Ilemhenbhio, F.; Pickering, G.A.E.; Kiss-Toth, E.; Wilkinson, J.M. Pathophysiology and Emerging Molecular Therapeutic Targets in Heterotopic Ossification. Int. J. Mol. Sci. 2022, 23, 6983. https://doi.org/10.3390/ijms23136983

AMA Style

Felix-Ilemhenbhio F, Pickering GAE, Kiss-Toth E, Wilkinson JM. Pathophysiology and Emerging Molecular Therapeutic Targets in Heterotopic Ossification. International Journal of Molecular Sciences. 2022; 23(13):6983. https://doi.org/10.3390/ijms23136983

Chicago/Turabian Style

Felix-Ilemhenbhio, Favour, George A.E. Pickering, Endre Kiss-Toth, and Jeremy M. Wilkinson. 2022. "Pathophysiology and Emerging Molecular Therapeutic Targets in Heterotopic Ossification" International Journal of Molecular Sciences 23, no. 13: 6983. https://doi.org/10.3390/ijms23136983

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