The molecular mechanism study of insulin on proliferation and differentiation of osteoblasts under high glucose conditions

Abstract

To explore the molecular mechanism of insulin on proliferation and differentiation of MC3T3‐E1 cell under high glucose conditions. We first investigated the effect of different concentrations of insulin on the osteoblast cell proliferation and cell differentiation at various time points by MTT analysis, cell cycle analysis, and expression detection of differentiation genes. Then, we used 200 ng/mL of insulin to treat the osteoblast cell at different time points for identifying the common differentially expressed mRNAs among various time points by RNA sequencing. Thirdly, we performed the gene ontology (GO) and the Kyoto Encyclopaedia of Genes and Genomes (KEGG) analysis to explore the biological function of these common differentially expressed mRNAs. The results showed that insulin promoted the cell proliferation and differentiation of osteoblast cell. In RNA sequencing, a total of 31 common differentially expressed mRNAs were identified between different time points. Mt1, Tmem135, Avp, and Dlg2 were found to be associated with the new bone formation. In addition, three important signalling pathways, namely, lysosome, glutamatergic synapse, and chemokine signalling pathways, were found in the KEGG enrichment analysis. Our work demonstrated that insulin could promote the osteoblast cell proliferation and cell differentiation, which may play a key role in bone formation. Significance of the study Our result showed that insulin could promote the proliferation and differentiation of osteoblast at both cellular and molecular levels, which may promote the new bone formation in the osteoblasts.

Gut microbiota is associated with bone mineral density

“…the tiny differences in demographic backgrounds may partly skew our results. thirdly, although the gut microbiota and gwei reported in this study are significantly related to l1-l4 Bmd, total Bmd, and femur total Bmd, which is consistent with some previous evidence, 43,51 further experimental studies are needed to explore and confirm the underlying molecular biological mechanisms. Finally, the gwas and gut microbiota data in this study were obtained from individuals of european ancestry, which should be applied to other races with care.…”

“…DLG2 was found to be associated with the new bone formation in RNA sequencing. 51 NFATC2 is important for the immune response, whereas NFATC1 is a crucial transcription factor for osteoclast differentiation and osteoclastogenesis in vitro. 52 Bone formation was inhibited in NFATC1- and NFATC2 -deficient cells, and stimulated in NFATC1 overexpression cells, suggesting that NFATC1 and NFATC2 were associated with osteoblastic bone formation and osteoporosis.…”

Circulating miRNAs in bone health and disease

“…and insulin growth factor 1 (IGF-1) [122,123]. Other co-factors leading to decreased bone formation include bone microarchitecture changes, increased bone marrow fat content, lowgrade inflammation, osteocyte dysfunction, and aggregation of advanced glycation end products (AGEs) in collagen due to hyperglycemia [124].…”

<p>Relationship Between Metabolic Syndrome and Bone Health – An Evaluation of Epidemiological Studies and Mechanisms Involved</p>

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