Chrdl2, encoding Chordin-like 2 protein, is a member of the chordin family and an inhibitor of BMP (bone morphogenetic protein) signaling [5]. It is involved in multiple biological processes such as cell proliferation, cell cycle regulation, and cell differentiation, and is thus of great biological importance. Genetic models are valuable for studying its functions in various biological contexts.

In cancer research, Chrdl2 has been extensively studied. In colorectal cancer, genetically predicted elevated levels of CHRDL2 are associated with an increased risk of the disease [1]. In gastric cancer, CHRDL2 is abnormally upregulated, positively associated with T stage, pathological stage, distant metastasis, and poor prognosis. Overexpressing CHRDL2 promotes the proliferation and cell cycle transition of gastric cancer cells by activating the YAP/TAZ pathway [2]. In osteosarcoma, CHRDL2 is upregulated in tissues and cell lines, and promotes cell proliferation and metastasis through the BMP-9/PI3K/AKT pathway [3]. In contrast, in steroid-induced avascular necrosis of the femoral head, CHRDL2 is down-regulated in necrosis of the femoral head samples and glucocorticoid-stimulated bone microvascular endothelial cells. Overexpression of CHRDL2 can improve glucocorticoid-caused cell apoptosis and dysfunctions via the PI3K/Akt pathway [4].

In conclusion, Chrdl2 plays crucial roles in cell proliferation, cell cycle, and differentiation processes. Through model-based research, its significance in cancer development, especially in colorectal, gastric, and osteosarcoma cancers, has been revealed. In addition, its role in bone-related diseases like steroid-induced avascular necrosis of the femoral head has also been demonstrated, providing potential therapeutic targets for these diseases.

References:

1. Sun, Jing, Zhao, Jianhui, Jiang, Fangyuan, Theodoratou, Evropi, Li, Xue. 2023. Identification of novel protein biomarkers and drug targets for colorectal cancer by integrating human plasma proteome with genome. In Genome medicine, 15, 75. doi:10.1186/s13073-023-01229-9. https://pubmed.ncbi.nlm.nih.gov/37726845/

2. Wang, Lingquan, Xu, Wei, Mei, Yu, Zhu, Zhenggang, Ni, Zhentian. 2022. CHRDL2 promotes cell proliferation by activating the YAP/TAZ signaling pathway in gastric cancer. In Free radical biology & medicine, 193, 158-170. doi:10.1016/j.freeradbiomed.2022.09.006. https://pubmed.ncbi.nlm.nih.gov/36206931/

3. Chen, Houping, Pan, Runsang, Li, Hao, Zhang, Xiangyan, Nie, Yingjie. 2021. CHRDL2 promotes osteosarcoma cell proliferation and metastasis through the BMP-9/PI3K/AKT pathway. In Cell biology international, 45, 623-632. doi:10.1002/cbin.11507. https://pubmed.ncbi.nlm.nih.gov/33245175/

4. Huang, Xianzhe, Jie, Shuo, Li, Wenzhao, Liu, Chan. 2024. CHRDL2 activates the PI3K/AKT pathway to ameliorate glucocorticoid-induced damages to bone microvascular endothelial cells (BMECs). In Heliyon, 10, e33867. doi:10.1016/j.heliyon.2024.e33867. https://pubmed.ncbi.nlm.nih.gov/39050472/

5. Potter, S Steven, Hartman, Heather A, Kwan, Kin M, Behringer, Richard R, Patterson, Larry T. . Laser capture-microarray analysis of Lim1 mutant kidney development. In Genesis (New York, N.Y. : 2000), 45, 432-9. doi:. https://pubmed.ncbi.nlm.nih.gov/17610272/