Osgin2-KO Mouse

Osgin2, an oxidative stress-induced factor, belongs to the Osgin gene family involved in the cellular oxidative stress response [7]. Although its biochemical role remains undefined, misregulation of Osgin2 has been associated with various diseases. It may play a part in pathways related to cell proliferation, apoptosis, and autophagy [7].

In osteoporotic rats, oxidative stress in jawbone bone marrow mesenchymal stem cells (BMSCs) is increased, along with up-regulation of Osgin2. Silence of Osgin2 ameliorates the declined osteogenesis of jawbone BMSCs under oxidative stress, restoring the expressions of RORα and its downstream osteogenic markers. Intra-jawbone infusion of si-OSGIN2 rescues jawbone loss and promotes new bone deposition [1]. In gastric cancer, high levels of Osgin2 in carcinoma cells and tissues are associated with a poor prognosis. Knockdown of Osgin2 inhibits tumor cell proliferation and causes cell cycle arrest [2]. In endothelial cells, the expression of Osgin2 is increased by cigarette smoke extract and TNFα under elevated flow, and knockdown of Osgin1&2 (including Osgin2) inhibits Nrf2-induced cell detachment [3]. In cadmium-exposed Tim-3 knockout mice, Osgin2 expression is affected, and Tim-3 deficiency aggravates cadmium nephrotoxicity [4]. In human dental-pulp-stem-cells-derived neurons, exposure to Ag-NPs changes the mRNA expression level of Osgin2 [5]. In soft-tissue sarcoma, miR-199a-5p regulates the 3'UTR of Osgin2 gene, and low miR-199a-5p expression is correlated with a poor patient outcome [6]. In colorectal cancer, Osgin2 is among the oxidative stress-related genes used to build a prognostic risk model [8]. In chicken breeds, Osgin2 is a candidate gene for cold adaptation [9]. In Ningqiang ponies, Osgin2 is associated with bone development [10].

In conclusion, Osgin2 is involved in multiple biological processes and disease conditions. Model-based research, such as gene knockdown experiments in different organisms, has revealed its role in osteogenesis, cancer cell proliferation, endothelial cell adhesion, cadmium-induced nephrotoxicity, and other biological functions related to oxidative stress, bone development, and environmental adaptation.

References:

1. Shuai, Yi, Liu, Bingyao, Rong, Liang, Chen, Bo, Jin, Lei. 2022. OSGIN2 regulates osteogenesis of jawbone BMSCs in osteoporotic rats. In BMC molecular and cell biology, 23, 22. doi:10.1186/s12860-022-00423-8. https://pubmed.ncbi.nlm.nih.gov/35729522/

2. Wang, Peipei, Zhu, Ying, Jia, Xinru, Sun, Leitao, Ruan, Shanming. 2023. Clinical prognostic value of OSGIN2 in gastric cancer and its proliferative effect in vitro. In Scientific reports, 13, 5775. doi:10.1038/s41598-023-32934-5. https://pubmed.ncbi.nlm.nih.gov/37031243/

3. Satta, Sandro, Beal, Robert, Smith, Rhys, Newby, Andrew C, White, Stephen J. . A Nrf2-OSGIN1&2-HSP70 axis mediates cigarette smoke-induced endothelial detachment: implications for plaque erosion. In Cardiovascular research, 119, 1869-1882. doi:10.1093/cvr/cvad022. https://pubmed.ncbi.nlm.nih.gov/36804807/

4. Yin, Guanyi, Wang, Zhonghang, Li, Peiyao, Li, Xuemiao, Lou, Qiang. 2024. Tim-3 deficiency aggravates cadmium nephrotoxicity via regulation of NF-κB signaling and mitochondrial damage. In International immunopharmacology, 128, 111434. doi:10.1016/j.intimp.2023.111434. https://pubmed.ncbi.nlm.nih.gov/38176346/

5. Bonaventura, Gabriele, La Cognata, Valentina, Iemmolo, Rosario, D'Agata, Velia, Cavallaro, Sebastiano. 2018. Ag-NPs induce apoptosis, mitochondrial damages and MT3/OSGIN2 expression changes in an in vitro model of human dental-pulp-stem-cells-derived neurons. In Neurotoxicology, 67, 84-93. doi:10.1016/j.neuro.2018.04.014. https://pubmed.ncbi.nlm.nih.gov/29698629/

6. Keßler, Jacqueline, Rot, Swetlana, Bache, Matthias, Taubert, Helge, Greither, Thomas. 2016. miR-199a-5p regulates HIF-1α and OSGIN2 and its expression is correlated to soft-tissue sarcoma patients' outcome. In Oncology letters, 12, 5281-5288. doi:10.3892/ol.2016.5320. https://pubmed.ncbi.nlm.nih.gov/28101243/

7. Hussey, Grace, Royster, Marcus, Vaidy, Nivedha, Culkin, Michael, Saha, Margaret S. 2025. The Osgin Gene Family: Underexplored Yet Essential Mediators of Oxidative Stress. In Biomolecules, 15, . doi:10.3390/biom15030409. https://pubmed.ncbi.nlm.nih.gov/40149945/

8. Chen, Zilu, Mei, Kun, Xiao, Yao, Gu, Renjun, Wang, Bin. 2022. Prognostic Assessment of Oxidative Stress-Related Genes in Colorectal Cancer and New Insights into Tumor Immunity. In Oxidative medicine and cellular longevity, 2022, 2518340. doi:10.1155/2022/2518340. https://pubmed.ncbi.nlm.nih.gov/36299603/

9. Romanov, Michael N, Abdelmanova, Alexandra S, Fisinin, Vladimir I, Griffin, Darren K, Zinovieva, Natalia A. 2023. Selective footprints and genes relevant to cold adaptation and other phenotypic traits are unscrambled in the genomes of divergently selected chicken breeds. In Journal of animal science and biotechnology, 14, 35. doi:10.1186/s40104-022-00813-0. https://pubmed.ncbi.nlm.nih.gov/36829208/

10. Han, Jiale, Shao, Hanrui, Sun, Minhao, Li, Na, Dang, Ruihua. 2025. Genomic insights into the genetic diversity and genetic basis of body height in endangered Chinese Ningqiang ponies. In BMC genomics, 26, 292. doi:10.1186/s12864-025-11484-2. https://pubmed.ncbi.nlm.nih.gov/40128652/