| First Author | Song S | Year | 2025 |
| Journal | Bone Res | Volume | 13 |
| Issue | 1 | Pages | 92 |
| PubMed ID | 41207902 | Mgi Jnum | J:378185 |
| Mgi Id | MGI:8278626 | Doi | 10.1038/s41413-025-00469-2 |
| Citation | Song S, et al. (2025) Descendants of hypertrophic chondrocytes promote angiogenesis by secreting THBS4 during bone growth and injury repair. Bone Res 13(1):92 |
| abstractText | Hypertrophic chondrocytes (HCs) could transform into osteoblastic lineage cells while the pathophysiological implications of HC transformation remain largely unknown. Here, we generated a mouse line utilizing Col10a1-Cre to induce DTA expression to genetically ablate HCs and their descendants. Col10a1-Cre; R26(DTA/+) mice displayed dwarf phenotype, abnormal spongy bone, and significantly delayed drill-hole injuries healing, suggesting an indispensable role of HC lineage extension in bone growth and injury repair. Intriguingly, single-cell RNA sequencing analysis revealed the most significant loss of a cell cluster expressing multiple angiogenic factors (Pro-Angiogenic Descendants of HCs, PADs) among cells derived from Col10a1-Cre; R26(DTA/+) and control femurs. In silico analysis of cell-cell communication supported Thrombospondin 4 (THBS4) as a specific angiogenic factor mediating the crosstalk between PADs and vascular endothelial cells. Concordantly, analyses using immunostaining combined with tissue clearing revealed that PADs physically contacted with endothelial cells, whereas Col10a1-Cre; R26(DTA/+) mice showed defective metaphyseal and cortical vessel formation and post-injury angiogenesis along with a significant loss of THBS4. Moreover, in vitro assays showed that supplying THBS4 was sufficient to promote proliferation and tube formation of endothelial cells and rescue defective angiogenesis of Col10a1-Cre; R26(DTA/+) metatarsal explants. Collectively, these findings demonstrate a critical role of PADs in bone growth and injury repair by secreting THBS4 to regulate angiogenesis. |
