Abstract
The precise regulation of chondrocyte differentiation is critical for endochondral ossification, and its disruption underlies a spectrum of skeletal diseases. While the Wnt/β-catenin signaling pathway is a well-established master regulator of skeletal development, its precise regulation during chondrogenesis remains incompletely understood. Here, we identify a novel regulatory axis centered on microRNA-205a and its target, the adhesion molecule Cadherin-11 (CDH11), in avian embryonic models. We demonstrate that CDH11 functions as a positive regulator of chondrocyte differentiation by promoting Wnt/β-catenin signaling. Conversely, miR-205a acts as a potent endogenous inhibitor of this process. Through dual-luciferase reporter assays, we confirm that miR-205a directly binds to the 3’UTR of CDH11 mRNA. Functional studies revealed that miR-205a overexpression suppresses chondrogenesis by downregulating CDH11, thereby inhibiting the Wnt/β-catenin pathway and key chondrogenic markers like Runx2 and BMP2. Silencing miR-205a or overexpressing CDH11 produced the opposite effect, promoting the differentiation program. Critically, rescue experiments using a Wnt/β-catenin pathway agonist substantiated that miR-205a exerts its inhibitory effects primarily through modulating this pathway. Our findings delineate a conserved miR-205a/CDH11/Wnt-β-catenin regulatory circuit that is essential for chondrocyte differentiation, offering fundamental new insights into the molecular etiology of cartilage development and its associated disorders.
Funding
This work was financially supported by the National Natural Science Foundation of China (32273073), the Xizang Natural Science Foundation (XZ202501ZR0025), Guangdong Provincial Specialty and Innovation Project for Regular Higher Education Institutions (2025KTSCX016), and the Specific university discipline construction project (2023B10564003).
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All methods were performed in accordance with the relevant guidelines and regulations. Primary tibial chondrocytes were isolated from chicken embryos. All procedures involving chicken embryos were reviewed and approved by the Animal Ethics Committee of South China Agricultural University, with the reference number 2022F045. This study did not involve human participants, human data, or identifiable human images; therefore, informed consent to participate and consent for publication were not applicable.
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Liu, K., Chen, B., Hou, J. et al. miR-205a mediated suppression of CDH11 disrupts Wnt/β-catenin signaling and impairs chondrocyte differentiation. Cell Death Discov. (2026). https://doi.org/10.1038/s41420-026-03146-3
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DOI: https://doi.org/10.1038/s41420-026-03146-3
