Galectin-3 Enhances Osteogenic Differentiation of Precursor Cells From Patients With Diffuse Idiopathic Skeletal Hyperostosis via Wnt/β-Catenin Signaling

Abstract

Diffuse idiopathic skeletal hyperostosis (DISH) is a noninflammatory skeletal disease characterized by the progressive ectopic ossification and calcification of ligaments and enthuses. However, specific pathogenesis remains unknown. Bone marrow mesenchymal stem cells (BMSCs) are a major source of osteoblasts and play vital roles in bone metabolism and ectopic osteogenesis. However, it is unclear whether BMSCs are involved in ectopic calcification and ossification in DISH. The current study aimed to explore the osteogenic differentiation abilities of BMSCs from DISH patients (DISH-BMSCs). Our results showed that DISH-BMSCs exhibited stronger osteogenic differentiation abilities than normal control (NC)-BMSCs. Human cytokine array kit analysis showed significantly increased secretion of Galectin-3 in DISH-BMSCs. Furthermore, Galectin-3 downregulation inhibited the increased osteogenic differentiation ability of DISH-BMSCs, whereas exogenous Galectin-3 significantly enhanced the osteogenic differentiation ability of NC-BMSCs. Notably, the increased Galectin-3 in DISH-BMSCs enhanced the expression of β-catenin as well as TCF-4, whereas attenuation of Wnt/β-catenin signaling partially alleviated Galectin-3-induced osteogenic differentiation and activity in DISH-BMSCs. In addition, our results noted that Galectin-3 interacted with β-catenin and enhanced its nuclear accumulation. Further in vivo studies showed that exogenous Galectin-3 enhanced ectopic bone formation in the Achilles tendon in trauma-induced rats by activating Wnt/βcatenin signaling. The current study indicated that enhanced osteogenic differentiation of DISH-BMSCs was mainly attributed to the increased secretion of Galectin-3 by DISH-BMSCs, which enhanced β-catenin expression and its nuclear accumulation. Our study helps illuminate the mechanisms of pathological osteogenesis and sheds light on the possible development of potential therapeutic strategies for DISH treatment.

HMGB1 Modulates High Glucose-Induced Erroneous Differentiation of Tendon Stem/Progenitor Cells through RAGE/β-Catenin Pathway

“…Moreover, treatment with HMGB1 remarkably increased the expression of RAGE in human BMSCs during osteogenic differentiation [ 27 ]. In addition, β -catenin interacts with TCF-4 in the nucleus to activate the transcription of osteogenic genes and has emerged as a critical regulator of the osteogenic differentiation of stem cells [ 30 – 32 ]. Increased RAGE could promote osteogenic differentiation of vascular smooth muscle cells and calcification via modulating downstream β -catenin signaling [ 53 , 54 ].…”

“…In addition, intracellular β -catenin signaling has emerged as a critical regulator of the osteogenic differentiation of stem cells [ 30 , 31 ]. In the nucleus, β -catenin is known to interact with transcription factor-4 (TCF-4) and activates the transcription of osteogenic genes [ 32 ]. Wang et al [ 33 ] showed that HMGB1 exerted a pro-osteogenic effect on human bone marrow-derived MSCs (BMSCs) via activating the β -catenin signaling.…”

The role of integrin family in bone metabolism and tumor bone metastasis

“…Mesenchymal stem cells (MSCs) are upstream progenitor cells with the ability to proliferate and differentiate [8]. Bone marrow mesenchymal stem cells (BMSCs) are important targets for studying bone-related diseases such as osteoporosis (OP), osteoarthritis (OA), and hyperostosis [9][10][11][12]. Integrins expression is dynamically regulated during BMSCs osteogenic differentiation.…”

The Role of Vitamin D in the Functioning of Bone Cells

“…У пошуках механізмів дії вітаміну D на остеокласти дослідники звернули увагу на галектин-3, нещодавно відкритий регулятор кісткового метаболізму, який бере участь у проліферації, диференціації та апоптозі різних типів клітин [63]. Фактор транскрипції галектин-3 у ядрі остеокластів розташований поряд з VDR.…”