Candidate kinases for adipogenesis and osteoblastogenesis from human bone marrow mesenchymal stem cells

Abstract

Adipogenesis and osteoblastogenesis (adipo-osteoblastogenesis) are closely related processes involving with the phosphorylation of numerous cytoplasmic proteins and key transcription factors. Despite the recognition of the importance of protein phosphorylation in adipo-osteoblastocyte biology, relatively little is known about the specific kinases for adipo-osteoblastogenesis. Here, we constructed the comprehensive gene transcriptional landscapes of kinases at 3, 5, and 7 days during adipo-osteoblastogenesis from human bone marrow mesenchymal stem cells (hMSCs). We identified forty-four and eight significant DEGs (differentially expressed genes) separately for adipo-osteoblastogenesis. Five significant DEGs, namely CAMK2A, NEK10, PAK3, PRKG2, and PTK2B, were simultaneously shared by adipo-osteoblastogenic anecdotes. Using a lentivirus system, we confirmed that PTK2B (non-receptor protein tyrosine kinase 2 beta) simultaneously inhibited adipo-osteoblastogenesis through RNAi assays, and PRKG2 (protein kinase cGMP-dependent 2) facilitated adipogenesis and weakened osteoblastogenesis. The only certainty was that the identified candidate significant DEGs encoding kinases responsible for protein phosphorylation, especially PTK2B and PRKG2, were the potential molecular switches of cell fate determination for hMSCs. This study would provide novel study targets for hMSC differentiation and potential clues for the therapy of the adipo-osteoblastogenic balance-derived disorders.