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 <i>CAMK2A</i>, <i>NEK10</i>, <i>PAK3</i>, <i>PRKG2</i>, and <i>PTK2B</i>, were simultaneously shared by adipo-osteoblastogenic anecdotes. Using a lentivirus system, we confirmed that <i>PTK2B</i> (non-receptor protein tyrosine kinase 2 beta) simultaneously inhibited adipo-osteoblastogenesis through RNAi assays, and <i>PRKG2</i> (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 <i>PTK2B</i> and <i>PRKG2</i>, 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.