Eisner Christine, Cummings Michael, Johnston Gabrielle, Tung Lin Wei, Groppa Elena, Chang Chihkai, Rossi Fabio Mv
Department of Medical Genetics, University of British Columbia, Vancouver, Canada.
Faculty of Medicine, The University of British Columbia, Vancouver, Canada.
J Bone Miner Res. 2020 Aug;35(8):1525-1534. doi: 10.1002/jbmr.4020. Epub 2020 Apr 16.
Acquired heterotopic ossifications (HO) arising as a result of various traumas, including injury or surgical interventions, often result in pain and loss of motion. Though triggers for HO have been identified, the cellular source of these heterotopic lesions as well as the underlying mechanisms that drive the formation of acquired HO remain poorly understood, and treatment options, including preventative treatments, remain limited. Here, we explore the cellular source of HO and a possible underlying mechanism for their spontaneous osteogenic differentiation. We demonstrate that HO lesions arise from tissue-resident PDGFRα+ fibro/adipogenic progenitors (FAPs) in skeletal muscle and not from circulating bone marrow-derived progenitors. Further, we show that accumulation of these cells in the tissue after damage due to alterations in the inflammatory environment can result in activation of their inherent osteogenic potential. This work suggests a mechanism by which an altered inflammatory cell and FAP interactions can lead to the formation of HO after injury and presents potential targets for therapeutics in acquired HO. © 2020 American Society for Bone and Mineral Research.
由包括损伤或外科手术干预在内的各种创伤引起的获得性异位骨化（HO），常常导致疼痛和活动受限。尽管已经确定了HO的触发因素，但这些异位病变的细胞来源以及驱动获得性HO形成的潜在机制仍知之甚少，包括预防性治疗在内的治疗选择也仍然有限。在此，我们探究了HO的细胞来源以及它们自发进行成骨分化的一种可能潜在机制。我们证明，HO病变源自骨骼肌中组织驻留的血小板衍生生长因子受体α阳性（PDGFRα+）成纤维/脂肪生成祖细胞（FAPs），而非循环的骨髓衍生祖细胞。此外，我们表明，由于炎症环境的改变，损伤后这些细胞在组织中的积累可导致其固有成骨潜能的激活。这项工作揭示了一种机制，即炎症细胞与FAPs之间相互作用的改变可导致损伤后HO的形成，并为获得性HO的治疗提供了潜在的治疗靶点。© 2020美国骨与矿物质研究学会。
