Role of Wnt5a in modulation of osteoporotic adipose-derived stem cells and osteogenesis

IF 5.9 1区 生物学 Q2 CELL BIOLOGY Cell Proliferation Pub Date : 2024-09-17 DOI:10.1111/cpr.13747
Lin Liu, Shihong Luo, Qiumei Li, Kui Huang, Yuan Jiang, Lu Zeng, Xiaorong Lan, Qing Li, Jingang Xiao
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Abstract

Osteoporosis, a condition marked by the deterioration of bone microarchitecture and increased facture risk, arises from a disruption in bone metabolism, with osteoclasts surpassing osteoblasts in bone resorption versus formation. The Wnt signalling pathway, a key regulator of bone maintenance, remains partially understood in osteoporosis. Our research delves into the role of Wnt-related molecules in this disease. In osteoporotic adipose-derived stem cells (OP-ASCs), we detected a significant decrease in Ctnnb1 and Frizzled-6 (Fzd6), contrasted by an increase in Gsk-3β and Wnt5a. Activation of the Wnt pathway by LiCl resulted in elevated Ctnnb1 and Fzd6, but decreased Gsk-3β and Wnt5a levels, promoting OP-ASCs' bone-formation capacity. In contrast, inhibition of this pathway by DKK-1 led to diminished Ctnnb1 and Fzd6, and increased Gsk-3β and Wnt5a, adversely affecting osteogenesis. Furthermore, our findings show that overexpressing Wnt5a impedes, while silencing it enhances the bone-forming capability of OP-ASCs. In a cranial bone defect model, the implantation of Wnt5a-silenced OP-ASCs with biphasic calcium phosphate scaffolds significantly promoted new bone formation. These observations indicated a repression of the canonical Wnt pathway and a stimulation of the non-canonical pathway in OP-ASCs. Silencing Wnt5a increased the osteogenic and regenerative abilities of OP-ASCs. Our study suggests targeting Wnt5a could be a promising strategy for enhancing bone regeneration in post-menopausal osteoporosis.

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Wnt5a 在调节骨质疏松性脂肪来源干细胞和成骨过程中的作用
骨质疏松症是一种以骨微结构退化和骨折风险增加为特征的疾病,它源于骨代谢紊乱,破骨细胞在骨吸收和骨形成中的作用超过了成骨细胞。Wnt 信号通路是骨维持的关键调节因子,但在骨质疏松症中的作用尚不明确。我们的研究深入探讨了 Wnt 相关分子在这种疾病中的作用。在骨质疏松症脂肪源性干细胞(OP-ASCs)中,我们检测到Ctnnb1和Frizzled-6(Fzd6)明显减少,而Gsk-3β和Wnt5a则有所增加。氯化锂激活Wnt通路会导致Ctnnb1和Fzd6升高,但Gsk-3β和Wnt5a水平降低,从而促进OP-ASCs的骨形成能力。相反,DKK-1对该通路的抑制导致Ctnnb1和Fzd6减少,Gsk-3β和Wnt5a增加,从而对骨形成产生不利影响。此外,我们的研究结果表明,过表达 Wnt5a 会阻碍 OP-ASCs 的成骨能力,而沉默 Wnt5a 则会增强 OP-ASCs 的成骨能力。在颅骨缺损模型中,将 Wnt5a 沉默的 OP-ASCs 植入双相磷酸钙支架能显著促进新骨形成。这些观察结果表明,在 OP-ASCs 中,规范 Wnt 通路受到抑制,而非规范通路受到刺激。沉默Wnt5a可提高OP-ASCs的成骨和再生能力。我们的研究表明,以Wnt5a为靶点可能是促进绝经后骨质疏松症患者骨再生的一种有前途的策略。
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来源期刊
Cell Proliferation
Cell Proliferation 生物-细胞生物学
CiteScore
14.80
自引率
2.40%
发文量
198
审稿时长
1 months
期刊介绍: Cell Proliferation Focus: Devoted to studies into all aspects of cell proliferation and differentiation. Covers normal and abnormal states. Explores control systems and mechanisms at various levels: inter- and intracellular, molecular, and genetic. Investigates modification by and interactions with chemical and physical agents. Includes mathematical modeling and the development of new techniques. Publication Content: Original research papers Invited review articles Book reviews Letters commenting on previously published papers and/or topics of general interest By organizing the information in this manner, readers can quickly grasp the scope, focus, and publication content of Cell Proliferation.
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