New insights into heterotopicossification: Progenitorcells play a key role in aberrant bone formation
cells to HO in our two injury models. The synovial membrane of the hip containsprogenitor cells that comprise approximately 40%–50% of the total aberrant bone area, while in the Achilles tendon, this represents approximately 20% of total bone cells. One reason for this may be the phenotype of the cells from distinct origins.
Moreover, the tissue-specific stroma and cartilage in the hip may release soluble molecules that further promote the expansion and differentiation ofprogenitor cells in different anatomical depots behave. This study has several limitations for consideration. First, our scRNA-seq data did not contain a reporter gene that can help trace the differentiation trajectory of cells. Second, the contribution and regulation of other cellular components, such as immune cells, blood vessels and nerves, were not assessed. For instance, previous reports from our group showed that HO is driven by coordinated growth of blood vessels and nerves.
Notably, in our scRNA-seq data, blood vessel-associated pericytes and nerve-associated Schwann cells both showedexpression, although these are both small cell populations in our models. In this context, there is no information on the effect or interaction of Tppp3which may indicate a more complex process regulating angiogenesis.
In conclusion, this study provides evidence of the contribution and regulatory potential of synovial/tendon sheath progenitorcells to form HO across traumatic injury models and the conserved cell identity in human HO samples. These novel observations have implications for the mechanisms that drive aberrant stem cell differentiation in soft tissues and possibly for the development and testing of new therapeutic strategies.
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