Undercarboxylated OCN promotes chondrogenesis of brown adipose-derived mesenchymal stem cells through Gprc6a

Abstract Background: The incidence of articular cartilage defects has significantly increased over the past few decades. Stem cell therapy treatment shows promise as an adjuvant to existing cartilage restoration techniques with improved short-term clinical outcomes and radiographic health of cartilage. Improving the ability of chondrogenesis of seed cells is an important link in the treatment of cartilage defects by tissue engineering. This study examined osteocalcin (OCN) changes during brown adipose stem cells (B-ADSCs) chondrogenesis. Methods: Brown adipose tissue was harvested from the middle of two scapulae of three days old neonatal C57B6NL mice. qRT-PCR, Western blot, and immunochemistry were used to assess differences in chondrogenesis markers. siRNA Gprc6a knockdown was used to assess whether undercarboxylated OCN (ucOCN) promotes chondrogenesis of B-ADSCs through Gprc6a. Results: Our study verified that B-ADSCs could secrete ucOCN during chondrogenesis. Also, ucOCN, but not carboxylated OCN (cOCN), could prominently promote the expression levels of chondrogenesis markers (SOX9, COL2a1, and ACAN). Mechanistically, ucOCN promoted chondrogenesis of B-ADSCs through Gprc6a. Conclusions: To sum up, ucOCN could promote chondrogenic differentiation of brown ADSCs through Gprc6a, which may provide a new strategy for applying stem cells in cartilage defect repair.