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Research Progress on the Mechanism of the SFRP-Mediated Wnt Signalling Pathway Involved in Bone Metabolism in Osteoporosis

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Abstract

Osteoporosis (OP) is a metabolic bone disease linked to an elevated fracture risk, primarily stemming from disruptions in bone metabolism. Present clinical treatments for OP merely alleviate symptoms. Hence, there exists a pressing need to identify novel targets for the clinical treatment of OP. Research indicates that the Wnt signalling pathway is modulated by serum-secreted frizzled-related protein 5 (SFRP5), potentially serving as a pivotal regulator in bone metabolism disorders. Moreover, studies confirm elevated SFRP5 expression in OP, with SFRP5 overexpression leading to the downregulation of Wnt and β-catenin proteins in the Wnt signalling pathway, as well as the expression of osteogenesis-related marker molecules such as RUNX2, ALP, and OPN. Conversely, the opposite has been reported when SFRP5 is knocked out, suggesting that SFRP5 may be a key factor involved in the regulation of bone metabolism via the Wnt signalling axis. However, the molecular mechanisms underlying the action of SFRP5-induced OP have yet to be comprehensively elucidated. This review focusses on the molecular structure and function of SFRP5 and the potential molecular mechanisms of the SFRP5-mediated Wnt signalling pathway involved in bone metabolism in OP, providing reasonable evidence for the targeted therapy of SFRP5 for the prevention and treatment of OP.

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Funding

This review gets grants from the National Natural Science Foundation of China (Grant No.82060872), the Scientific Research Program of Gansu Chinese Medicine Bureau (Grant GZKP-2023-39, and GZKP-2023-63), Research and Reform Project of Graduate Education and Teaching at Gansu University of Chinese Medicine (Grant 15), Teaching Research and Reform Project of Gansu University of Chinese Medicine (Grant YBXM-202332, and ZHXM-202307), and Gansu Province Higher Education Youth Doctoral Fund Project (Grant No.2022QB-091).

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  1. Fangyu An and Jiayi Song have equally contributed co-frst authors.

Authors and Affiliations

  1. Teaching Experiment Training Center, Gansu University of Chinese Medicine, Lanzhou, 730000, Gansu, China

    Fangyu An

  2. School of Basic Medicine, Gansu University of Chinese Medicine, Lanzhou, 730000, Gansu, China

    Jiayi Song, Weirong Chang, Jie Zhang & Peng Gao

  3. School of Traditional Chinese and Western Medicine, Gansu University of Chinese Medicine, Lanzhou, 730000, Gansu, China

    Yujie Wang, Zhipan Xiao & Chunlu Yan

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The conception and design of this manuscript was completed by CY. The first draft of this manuscript was written by FA and JS, and FA, JS are co-first authors. The figures and table of the manuscript were made by WC, JZ, PG, YW, and ZX. All authors have read and approved the final manuscript.

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Correspondence to Chunlu Yan.

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An, F., Song, J., Chang, W. et al. Research Progress on the Mechanism of the SFRP-Mediated Wnt Signalling Pathway Involved in Bone Metabolism in Osteoporosis. Mol Biotechnol 66, 975–990 (2024). https://doi.org/10.1007/s12033-023-01018-0

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