Sfrp4, Secreted Frizzled Receptor Protein 4, is a decoy receptor for Wnt ligands and an antagonist of WNT signaling [1,4,6,7]. It is involved in multiple biological processes, including bone development, endometrial regeneration, ovarian function, and is associated with diseases like Pyle disease, atherosclerosis, and polycystic ovary syndrome (PCOS) [1,3,4,5,6]. Genetic models, such as gene knockout mice, are crucial for studying its functions.

In bone, Sfrp4-null mice exhibit cortical bone thinning seen in Pyle disease, with impaired periosteal apposition due to decreased periosteal stem cell (PSC) pool and their clonal multipotency [1,2]. In the ovary, Sfrp4-null female mice are hyperfertile due to decreased antral follicle atresia and enhanced ovulatory rate, as SFRP4 normally attenuates granulosa cell responsiveness to gonadotropins [7]. Also, in IR-induced PCOS models, SFRP4 contributes to the pathogenesis by triggering ovarian granulosa cell hyperandrogenism and apoptosis through the nuclear β-catenin/IL-6 signaling axis [6].

In summary, Sfrp4 plays essential roles in bone development, ovarian function, and is involved in disease-related processes like PCOS. Gene knockout mouse models have been instrumental in revealing these functions, providing insights into the underlying mechanisms and potential therapeutic targets for related diseases.

References:

1. Chen, Ruiying, Baron, Roland, Gori, Francesca. 2022. Sfrp4 and the Biology of Cortical Bone. In Current osteoporosis reports, 20, 153-161. doi:10.1007/s11914-022-00727-w. https://pubmed.ncbi.nlm.nih.gov/35182301/

2. Chen, Ruiying, Dong, Han, Raval, Dhairya, Greenblatt, Matthew B, Gori, Francesca. 2023. Sfrp4 is required to maintain Ctsk-lineage periosteal stem cell niche function. In Proceedings of the National Academy of Sciences of the United States of America, 120, e2312677120. doi:10.1073/pnas.2312677120. https://pubmed.ncbi.nlm.nih.gov/37931101/

3. Wu, Bingbing, Li, Yu, Nie, Nanfang, Qian, Jianhua, Zou, XiaoHui. 2022. SFRP4+ stromal cell subpopulation with IGF1 signaling in human endometrial regeneration. In Cell discovery, 8, 95. doi:10.1038/s41421-022-00438-7. https://pubmed.ncbi.nlm.nih.gov/36163341/

4. Bérubé, Michael, Abedini, Atefeh, Lapointe, Evelyne, Zamberlam, Gustavo, Boerboom, Derek. 2024. SFRP4 promotes autophagy and blunts FSH responsiveness through inhibition of AKT signaling in ovarian granulosa cells. In Cell communication and signaling : CCS, 22, 396. doi:10.1186/s12964-024-01736-1. https://pubmed.ncbi.nlm.nih.gov/39138534/

5. Guan, Hua, Liu, Ting, Liu, Miaomiao, Shi, Tao, Guo, Fengwei. 2023. SFRP4 Reduces Atherosclerosis Plaque Formation in ApoE Deficient Mice. In Cardiology research and practice, 2023, 8302289. doi:10.1155/2023/8302289. https://pubmed.ncbi.nlm.nih.gov/37143778/

6. Wang, Jiangxia, Gui, Runlin, Li, Yang, Fan, Xiaobin, Xiong, Yuyan. 2024. SFRP4 contributes to insulin resistance-induced polycystic ovary syndrome by triggering ovarian granulosa cell hyperandrogenism and apoptosis through the nuclear β-catenin/IL-6 signaling axis. In Biochimica et biophysica acta. Molecular cell research, 1871, 119822. doi:10.1016/j.bbamcr.2024.119822. https://pubmed.ncbi.nlm.nih.gov/39159685/

7. Zamberlam, Gustavo, Lapointe, Evelyne, Abedini, Atefeh, DeMayo, Francesco J, Boerboom, Derek. . SFRP4 Is a Negative Regulator of Ovarian Follicle Development and Female Fertility. In Endocrinology, 160, 1561-1572. doi:10.1210/en.2019-00212. https://pubmed.ncbi.nlm.nih.gov/30942852/