Dynamic expression of SMAD3 is critical in�osteoblast differentiation of PDMCs

Abstract

Human pluripotent stem cells have the potential assist in the identification of genes involved in mammalian development. The human placenta is considered a repository of stem cells, termed placenta-derived multipotent cells (PDMCs), which are able to differentiate into cells with an osteoblastic phenotype. This plasticity of PDMCs maybe applied clinically to the understanding of osteogenesis and osteoporosis. In the presentstudy, osteoblasts were generated by culturing PDMCs in osteogenic medium. Reverse transcription quantitative polymerase chain reactionand the degree of osteoblast calcification were used to evaluate the efficacy of osteogenesis. The results suggestedthat the expression of mothers against decapentaplegic homolog 3 (SMAD3) increased in the initial stages of osteogenic differentiation but decreased in the later stages. However, osteogenesis was inhibitedwhen the PDMCs overexpressed SMAD3 throughout the differentiation period. In addition, the rate of osteogenic differentiation was decreased when SMAD3 signaling was impaired. In conclusion, SMAD3 serves an important role in osteoblast differentiation and bone formation in a time-dependent manner. The data from the present study indicate that arapid increase in SMAD3 expression is crucial for osteogenesis and suggest a role for PDMCs in the treatment of patients with osteoporosis.

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“…In agreement with our observation, BMP2 was shown to activate SMAD3-dependent signaling (Ongaro et al, 2019). Transcription factor SMAD3 expression is crucial for osteogenesis and the skeletal development process (Lin et al, 2019). Some studies have demonstrated that TGF-β3 also recruits endogenous human MSCs to initiate bone regeneration.…”

MiR-596 inhibits osteoblastic differentiation and cell proliferation by targeting Smad3 in steroid-induced osteonecrosis of femoral head

“…For example, Borton et al revealed that Smad3 knockout mice had osteopenia after weaning [23]. Additionally, Smad3 can also participate in the proliferation and osteogenic differentiation of BMSCs [24]. Previous studies have suggested that lncRNA H19 can promote BMSC osteogenic differentiation, which is related to Smad3 [25].…”

Lineage-selective super enhancers mediate core regulatory circuitry during adipogenic and osteogenic differentiation of human mesenchymal stem cells

“…As illustrated in Fig. 5A , the key TFs that have been widely proved to be involved in osteogenesis ( SMAD3 [ 43 ], FOXO1 [ 44 ], SOX4 [ 45 ]) and adipogenesis ( PPARG [ 46 ], EBF1 [ 47 ], CEBPB [ 48 ]) were specifically enriched in osteoblasts-selective and adipocytes-selective SEs sets, respectively, suggesting the vital roles of master TFs in the establishment of SEs. Notably, among these enriched TFs, four TFs ( FLI1 and ETS1 for osteoblasts, NFIL3 and RXRA for adipocytes) were also regulated by lineage-selective SEs (Fig.…”