| Human bone marrow stem cells(BMSCs)are heterogeneous progenitor cells with two defining features,self-renew and multi-lineage differentiation.They exhibit great capacity to differentiate into numerous mature cell types under the guidance of several factors including microenvironment,molecular and genetic mediators.Osteoblasts,as one of the products of BMSCs differentiation,play a key role in bone formation and bone homeostasis.The dysfunction of BMSCs osteogenic differentiation will lead to bone metabolism-related diseases Thus,it is crucial to elucidate the underlying mechanism of BMSCs osteogenic differentiation.In this study we acquired and analyzed the dataset GSE80614,which includes m RNA expression profile of BMSCs during the osteogenic differentiation process.We found that LMCD1 expression is upregulated during the osteogenic differentiation process of BMSCs by comparing the gene expression at the differentiation time of 3 or4 days with that at 0 or 0.5 h.In vitro and in vivo functional studies confirmed that LMCD1 was critical to the osteogenic commitment of BMSCs.Mechanically,we found that LMCD1 could protect RUNX2 and Smad1 protein from Smurf1-induced ubiquitination degradation thereby regulating BMP signaling.Similarly,we identified that the expression of CRYAB was upregulated during the osteogenic differentiation process of BMSCs when comparing the differentiation time of 3 or 4 days to that of 1or 2 hours.And the essential role of CRYAB in the osteogenic differentiation of BMSCs was also confirmed by in vitro and in vivo functional studies.In addition,we found that CRYAB could physically interact with ?-catenin and protect it from ubiquitination and degradation,which stabilized ?-catenin and promoted the Wnt signaling.In conclusion,we discovered the essential role of LMCD1 and CRYAB in the osteogenic differentiation of BMSCs.They may serve as potential therapeutic targets for diseases related to bone metabolism. |
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