LMCD1 promotes osteogenic differentiation of human bone marrow stem cells by regulating BMP signaling

Human bone marrow stem cells (BMSCs) are heterogeneous progenitor cells with two defining features, self-renew and multi-lineage differentiation. As one of the differentiation directions, osteogenesis is vital for bone homeostasis. A growing body of evidences show that ubiquitin-dependent protein degradation plays an essential role in the osteogenic differentiation of BMSCs. In this study, we found that LMCD1 was upregulated during osteogenic differentiation process of BMSCs by analyzing GSE80614. In vitro and in vivo functional studies confirmed that LMCD1 was critical to the osteogenic commitment of BMSCs. Compared to those of the controls, downregulation of LMCD1 significantly restrained osteogenic differentiation and enhanced adipogenic differentiation, while upregulation of LMCD1 increased the osteogenic differentiation and suppressed adipogenic differentiation. Mechanically, we found that LMCD1 could protect RUNX2 and Smad1 protein from Smurf1-induced ubiquitination degradation thereby regulating BMP signaling. In conclusion, our findings suggest that LMCD1 is a novel regulator of osteogenic differentiation and may be a potential therapeutic target for bone metabolism related diseases.