Murine Tissue-Resident PDGFRα plus Fibro-Adipogenic Progenitors Spontaneously Acquire Osteogenic Phenotype in an Altered Inflammatory Environment
Murine Tissue-Resident PDGFRα plus Fibro-Adipogenic Progenitors Spontaneously Acquire Osteogenic Phenotype in an Altered Inflammatory Environment
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DOI：
10.1002/jbmr.4020
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发表时间：
2020-04-16
影响因子：
6.2
通讯作者：
Rossi, Fabio M., V
中科院分区：
文献类型：
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作者：
Eisner, Christine;Cummings, Michael;Rossi, Fabio M., V
获得性异位骨化(获得性异位骨化)是由各种创伤引起的，包括创伤或手术干预，通常会导致疼痛和运动障碍。尽管HO的诱因已经确定，但这些异位病变的细胞来源以及导致获得性HO形成的潜在机制仍然知之甚少，包括预防性治疗在内的治疗选择仍然有限。在这里，我们探索HO的细胞来源和其自发成骨分化的可能潜在机制。我们证明HO损伤是由骨骼肌中的组织驻留的PDGFRα+纤维/脂肪前体细胞(FAP)引起的，而不是来自循环中的骨髓来源的前体细胞。此外，我们还表明，由于炎症环境的改变，这些细胞在损伤后在组织中的积累可以导致它们固有的成骨潜力的激活。这项工作提出了一种机制，通过改变炎症细胞和FAP的相互作用，可以导致损伤后HO的形成，并为获得性HO的治疗提供了潜在的靶点。(C)2020年美国骨与矿物研究学会。
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 PDGFR alpha+ 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. (c) 2020 American Society for Bone and Mineral Research.