Inhibition of TGF‐β type I receptor by SB505124 down‐regulates osteoblast differentiation and mineralization of human mesenchymal stem cells

Abstract

Numerous signaling pathways are well‐known in osteoblastic differentiation of human bone marrow mesenchymal stem cells (hBMSCs), including transforming growth factor‐beta (TGF‐β) signaling pathway, which sends signals through specific type I and II serine/threonine kinase receptors. However, the key role of TGF‐β signaling during bone formation and remodeling is yet to be studied. A TGF‐β type I receptor inhibitor, SB505124, discovered through a screening of a small molecule library for their effect of osteoblast differentiation of hBMSCs. Alkaline phosphatase quantification and staining were tested as indicators of osteoblastic differentiation and Alizarin red staining was tested as an indicator of in vitro mineralization. Changes in gene expressions were assessed using qRT‐PCR. SB505124 showed significant inhibition of the osteoblast differentiation of hBMSCs, as confirmed by reduced alkaline phosphatase, in vitro mineralization, and downregulation of osteoblast‐associated gene expression. To further understand the molecular mechanisms involved in the inhibition of the TGF‐β type I receptor, we assessed the effects on signature genes of several signaling pathways identified in the osteoblast differentiation of hBMSCs. SB505124 downregulated gene expression of many genes linked to osteoblast‐related signaling pathways including TGF‐β, insulin, focal adhesion, Notch, Vitamin D, interleukin (IL)‐6, osteoblast signaling, and cytokines and inflammatory. We report TGF‐β type I receptor inhibitor (SB505124) is a potent inhibitor of osteoblastic differentiation of hBMSCs that could be a valuable innovative therapeutic tool to cure bone disorders with increased bone formation, besides its potential use to treat patients with cancer and fibrosis.

Molecular mechanism of a novel root-end filling material containing zirconium oxide on the osteogenic/odontogenic differentiation of human osteosarcoma MG-63 cells

“…The TGF-β signaling pathway plays a crucial role in various cellular functions, including proliferation, apoptosis, differentiation, and migration. During osteogenic differentiation, the TGF-β signaling pathway transmits signals through type I and type II serine/threonine kinase receptors ( Almuraikhi, 2023 ).…”

“…The TGF-β signaling pathway plays a crucial role in various cellular functions, including proliferation, apoptosis, differentiation, and migration. During osteogenic differentiation, the TGF-β signaling pathway transmits signals through type I and type II serine/threonine kinase receptors (Almuraikhi, 2023). (2)MAPK signaling pathway 4 genes favored osteogenic differentiation, while 3 genes hindered osteogenic differentiation 2 genes promoted osteogenic differentiation and 2 genes hindered osteogenic differentiation…”