Abstract
Osteoporosis is a skeletal disease that is both systemic and silent characterized by an unbalanced activity of bone remodeling leading to bone loss. Rising evidences demonstrate that thyroid stimulating hormone (TSH) has an important role in the regulation on the metabolism of bone. However, TSH regulation on human osteoblast essential transcriptional factors has not been identified. Current study examined the role of TSH on human osteoblastic Runx2 expression and their functional genes by in vitro and in slico analysis. Human osteoblast like (HOS and SaoS-2) cells were cultured with DMEM and treated with hTSH at the concentration of 0.01 ng/mL and 10 ng/mL. After treatment, osteoblastic Runx2 and IGF-1R beta expression were studied using RT-PCR and western blot analysis. TSH treatment induced osteoblastic essential transcriptional factor, Runx2 in HOS and SaOS2 cells on 48 h duration and elevated the expression of IGF-IR β gene and Protein in SaoS-2 cells. TSH also promotes Runx2 responsive genes such as ALP, Collagen and osteocalcin in SaOS2 cells on day 2 to day 14 of 10 ng/mL of treatment and favors’ matrix mineralization matrix in these cells. In addition, TSH facilitated human osteoblastic cells to mineralize their matrix confirmed by day 21 of alizarin red calcium staining. In silico study was performed to check CREB and ELK1 interaction with Runx2. Results of in silico analysis showed that TSH mediated signalling molecules such as CREB and ELK1 showed interaction with Runx2 which involve in osteobalstic gene expression and differentiation. Present findings confirm that TSH promotes Runx2 expression, osteoblastic responsive genes and bone matrix formation.
Highlights
Thyroid stimulating hormone (TSH) is known to regulate bone metabolism and their biologically active receptors present in the cells of bone
The present study investigated the role of human TSH in bone-forming osteoblastic transcriptional factor Runx2 and its functional genes such as ALP, collagen, and OCN, and matrix mineralization in human osteoblasts such as SaOS-2 and HOS cells in vitro
It’s reasonable to presume that TSH would have enhanced Runx2 expression in HOS and SaOS-2 cells by activating Protein kinase A (PKA) signalling pathways
Summary
Thyroid stimulating hormone (TSH) is known to regulate bone metabolism and their biologically active receptors present in the cells of bone. Stimulation of the TSH receptor (TSHR) in osteoclast, suppresses the resorption of bone [1]. Administration of TSH intermittently stimulates osteoblastic bone formation and prevents ovariectomy-induced bone loss [2–4]. TSH is found to generate T3 through increased expression of deiodinase in human osteoblast like SaOS-2 cells [5]. It promotes osteoblast development in U2OS cells, which is mediated in part by activator signals via β-arrestin-1 [11]. TSH was found to inhibit osteoclast formation and survival through TSHR expressed in these cells. Clinical experiment by Mazziott et al [4] found that a single subcutaneous injection of recombinant human TSH to postmenopausal osteoporotic women drastically lowers serum C-telopeptide, a marker of bone resorption and facilitates bone formation
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