Col10a1, which encodes the α‑1 chain of type X collagen, is crucial for conferring tensile strength and structural integrity to tissues [2]. It is involved in multiple signaling pathways such as TGF‑β1/Smad, MEK/ERK, and focal adhesion kinase signaling pathways [2]. Genetic models, like KO/CKO mouse models, can be valuable for studying its function.

In osteoarthritis (OA), miR-26b-5p can target COL10A1, inhibiting chondrocyte hypertrophy induced by M1 macrophage-conditioned medium and alleviating OA progression [1]. In pancreatic adenocarcinoma, knockdown of COL10A1 inhibited cell proliferation, migration, and invasion, suggesting its role in promoting tumorigenesis [3]. In colon cancer, COL10A1 is overexpressed, correlates with poor patient survival, and may be a potential biomarker for immunotherapy [4]. In breast cancer, knockdown of COL10A1 suppressed cell proliferation, migration, and invasion, and promoted apoptosis [5]. In pancreatic cancer, COL10A1 binds to DDR2 to regulate cell proliferation, migration, invasion, and EMT through the MEK/ERK signaling pathway [6]. In Schmid-type metaphyseal chondrodysplasia, a rare autosomal dominant skeletal dysplasia, heterozygous mutations in COL10A1 are causative [7].

In conclusion, Col10a1 plays essential roles in maintaining tissue structure and is involved in various disease processes, including OA, multiple types of cancer, and skeletal dysplasia. Studies using gene knockout or knockdown models have revealed its role in promoting disease progression in cancer and chondrocyte hypertrophy in OA, highlighting its potential as a therapeutic target in these disease areas.

References:

1. Qian, Yufan, Chu, Genglei, Zhang, Lei, Guo, Jiong Jiong, Zhou, Feng. 2024. M2 macrophage-derived exosomal miR-26b-5p regulates macrophage polarization and chondrocyte hypertrophy by targeting TLR3 and COL10A1 to alleviate osteoarthritis. In Journal of nanobiotechnology, 22, 72. doi:10.1186/s12951-024-02336-4. https://pubmed.ncbi.nlm.nih.gov/38374072/

2. Yi, Qiang, Zhu, Gangfeng, Zhu, Weijian, Yang, Kuan, Zhong, Jinghua. 2024. Oncogenic mechanisms of COL10A1 in cancer and clinical challenges (Review). In Oncology reports, 52, . doi:10.3892/or.2024.8821. https://pubmed.ncbi.nlm.nih.gov/39392043/

3. Xu, Qiaodong, Zheng, Jieting, Su, Zegeng, Chen, Binlie, Gu, Songgang. 2023. COL10A1 promotes tumorigenesis by modulating CD276 in pancreatic adenocarcinoma. In BMC gastroenterology, 23, 397. doi:10.1186/s12876-023-03045-2. https://pubmed.ncbi.nlm.nih.gov/37974070/

4. Cai, Shuo, Sun, Zhiwei, Yan, Yan, Li, Weifeng, Wu, Qi. 2023. COL10A1 is a potential immunotherapy biomarker associated with immune infiltration and deficient mismatch repair in colon cancer. In Immunotherapy, 15, 1293-1308. doi:10.2217/imt-2023-0096. https://pubmed.ncbi.nlm.nih.gov/37585671/

5. Zhou, Weijian, Li, Yuting, Gu, Dingyi, Wang, Huiyu, Liu, Chaoying. 2022. High expression COL10A1 promotes breast cancer progression and predicts poor prognosis. In Heliyon, 8, e11083. doi:10.1016/j.heliyon.2022.e11083. https://pubmed.ncbi.nlm.nih.gov/36281404/

6. Wen, Zhihui, Sun, Jingbo, Luo, Junjie, Wu, Hongmei, Zhang, Qingling. 2022. COL10A1-DDR2 axis promotes the progression of pancreatic cancer by regulating MEK/ERK signal transduction. In Frontiers in oncology, 12, 1049345. doi:10.3389/fonc.2022.1049345. https://pubmed.ncbi.nlm.nih.gov/36530986/

7. Wu, Huixiao, Wang, Shuping, Li, Guimei, Wang, Yanzhou, Xu, Chao. 2021. Characterization of a novel COL10A1 variant associated with Schmid-type metaphyseal chondrodysplasia and a literature review. In Molecular genetics & genomic medicine, 9, e1668. doi:10.1002/mgg3.1668. https://pubmed.ncbi.nlm.nih.gov/33764685/