Tnfrsf11b, also known as osteoprotegerin, is a protein-coding gene. It plays a crucial role in multiple biological processes, being closely involved in signal transduction, immune response, and inflammatory response [1]. It is part of the RANKL/RANK/OPG pathway which is significant in bone remodeling [4,6,8].

In sepsis-ARDS, TNFRSF11B levels are significantly elevated compared to healthy controls. Its increase is associated with vascular endothelial dysfunction, as seen by changes in the levels of proteins related to endothelial function in TNFRSF11B-stimulated HUVECs [1]. In osteoarthritic cartilage, overexpression of TNFRSF11B may drive chondrocyte to osteoblast transition, not via the OPG/RANK/RANKL triad commonly seen in bone remodeling [2]. In gastric cancer, TNFRSF11B is highly expressed in the cytoplasm, promoting cell proliferation, migration, invasion, and inhibiting apoptosis by activating the Wnt/β-catenin signaling pathway [3]. In obstructive sleep apnea, plasma TNFRSF11B levels are significantly higher and are associated with the presence and severity of the disease, suggesting it could be a biomarker for endothelial dysfunction [5]. In colon cancer, TNFRSF11B acts as a prognostic factor, related to lymph node invasion, pathogenic E. coli infection, and suppressing memory CD4+ T cell infiltration in the cancer microenvironment [7]. Polymorphisms in TNFRSF11B are associated with an increased risk of short-term poor outcome in large artery atherosclerosis stroke [9].

In conclusion, Tnfrsf11b is essential in processes like inflammation, bone remodeling, and cancer progression. Studies related to Tnfrsf11b, though not specifically highlighting KO/CKO mouse models in the provided references, have shed light on its role in various disease conditions such as sepsis-ARDS, osteoarthritis, gastric cancer, obstructive sleep apnea, colon cancer, and large artery atherosclerosis stroke. Understanding Tnfrsf11b provides insights into disease mechanisms and potential biomarker and therapeutic targets.

References:

1. Zhang, Dong, Xu, Changjuan, Zhang, Jintao, Zhang, Jianning, Dong, Liang. 2023. Plasma TNFRSF11B as a New Predictive Inflammatory Marker of Sepsis-ARDS with Endothelial Dysfunction. In Journal of proteome research, 22, 3640-3651. doi:10.1021/acs.jproteome.3c00576. https://pubmed.ncbi.nlm.nih.gov/37851947/

2. Rodríguez Ruiz, Alejandro, Tuerlings, Margo, Das, Ankita, Ramos, Yolande F M, Meulenbelt, Ingrid. . The role of TNFRSF11B in development of osteoarthritic cartilage. In Rheumatology (Oxford, England), 61, 856-864. doi:10.1093/rheumatology/keab440. https://pubmed.ncbi.nlm.nih.gov/33989379/

3. Luan, Fengming, Li, Xiaomei, Cheng, Xiaojing, Wen, Xianzi, Ji, Jiafu. 2020. TNFRSF11B activates Wnt/β-catenin signaling and promotes gastric cancer progression. In International journal of biological sciences, 16, 1956-1971. doi:10.7150/ijbs.43630. https://pubmed.ncbi.nlm.nih.gov/32398963/

4. Boyle, William J, Simonet, W Scott, Lacey, David L. . Osteoclast differentiation and activation. In Nature, 423, 337-42. doi:. https://pubmed.ncbi.nlm.nih.gov/12748652/

5. Wen, Wan-Wan, Ning, Yu, Zhang, Qing, Zhang, Ming, Wei, Yong-Xiang. 2018. TNFRSF11B: A potential plasma biomarker for diagnosis of obstructive sleep apnea. In Clinica chimica acta; international journal of clinical chemistry, 490, 39-45. doi:10.1016/j.cca.2018.12.017. https://pubmed.ncbi.nlm.nih.gov/30562485/

6. Teitelbaum, S L. . Bone resorption by osteoclasts. In Science (New York, N.Y.), 289, 1504-8. doi:. https://pubmed.ncbi.nlm.nih.gov/10968780/

7. Zhang, Jun-Rong, Hou, Ping, Wang, Xiao-Jie, Huang, Zheng-Yuan, Chen, Xian-Qiang. 2021. TNFRSF11B Suppresses Memory CD4+ T Cell Infiltration in the Colon Cancer Microenvironment: A Multiomics Integrative Analysis. In Frontiers in immunology, 12, 742358. doi:10.3389/fimmu.2021.742358. https://pubmed.ncbi.nlm.nih.gov/34938284/

8. Tobeiha, Mohammad, Moghadasian, Mohammed H, Amin, Negin, Jafarnejad, Sadegh. 2020. RANKL/RANK/OPG Pathway: A Mechanism Involved in Exercise-Induced Bone Remodeling. In BioMed research international, 2020, 6910312. doi:10.1155/2020/6910312. https://pubmed.ncbi.nlm.nih.gov/32149122/

9. Wang, Mengmeng, Gu, Mengmeng, Li, Zibao, Zhang, Zhizhong, Liu, Xinfeng. 2020. TNFRSF11B polymorphisms predict poor outcome after large artery atherosclerosis stroke. In Gene, 743, 144617. doi:10.1016/j.gene.2020.144617. https://pubmed.ncbi.nlm.nih.gov/32222535/