Mir140-KO Mouse

MicroRNA-140 (miR-140) is a critical non-coding RNA molecule that plays a pivotal role in various biological processes, particularly in skeletal development and cartilage maintenance. miR-140 is specifically expressed in chondrocytes, the cells responsible for cartilage formation and maintenance, and its expression is essential for normal skeletal development. Dysregulation of miR-140 has been linked to skeletal dysplasias, such as those caused by mutations in miR-140 and miR-17~92 miRNAs [5]. These dysplasias highlight the importance of miR-140 in regulating gene expression and maintaining the structural integrity of the skeleton.

In addition to its role in skeletal development, miR-140 has been implicated in the pathogenesis of osteoarthritis (OA), a chronic musculoskeletal disorder characterized by the degeneration of joint cartilage and the underlying bone. Studies have shown that miR-140 is involved in the regulation of chondrocyte function, including proliferation, migration, apoptosis, and extracellular matrix (ECM) secretion. For example, exosomes derived from human urine-derived stem cells (hUSCs) overexpressing miR-140-5p have been shown to alleviate knee OA by downregulating vascular endothelial growth factor A (VEGFA), a key factor in OA progression [3]. Moreover, the delivery of miR-140 to chondrocytes using engineered exosomes has been demonstrated to enhance cartilage regeneration and subchondral bone remodeling in a rat OA model, further highlighting its therapeutic potential [6].

miR-140 is also involved in the regulation of cell fate and differentiation. In obesity, miR-140 has been shown to promote adipogenesis and contribute to bone deterioration by targeting the Pparα-Abca1 axis in skeletal stem/progenitor cells (SSPCs) [2]. This finding suggests that miR-140 may play a role in the pathogenesis of obesity-related bone disorders by influencing the differentiation of SSPCs.

Furthermore, miR-140 has been implicated in the regulation of inflammation and immune responses. For example, downregulation of miR-140 has been associated with cancer cell survival and escape from stresses, highlighting its potential role in tumor progression [1]. Additionally, miR-140 has been shown to regulate the immune response in rheumatoid arthritis (RA) and OA, further underscoring its importance in immune-related diseases [4].

Overall, miR-140 is a crucial regulator of skeletal development, cartilage maintenance, and immune responses. Its dysregulation has been linked to various diseases, including skeletal dysplasias, OA, and cancer. Further research is needed to fully understand the mechanisms by which miR-140 functions and its potential therapeutic applications in the treatment of these diseases.

References:

1. Ginckels, Pieterjan, Holvoet, Paul. 2022. Oxidative Stress and Inflammation in Cardiovascular Diseases and Cancer: Role of Non-coding RNAs. In The Yale journal of biology and medicine, 95, 129-152. doi:. https://pubmed.ncbi.nlm.nih.gov/35370493/

2. He, Chen, Hu, Chen, He, Wen-Zhen, Lei, Guang-Hua, Li, Chang-Jun. 2024. Macrophage-derived extracellular vesicles regulate skeletal stem/progenitor Cell lineage fate and bone deterioration in obesity. In Bioactive materials, 36, 508-523. doi:10.1016/j.bioactmat.2024.06.035. https://pubmed.ncbi.nlm.nih.gov/39072285/

3. Liu, Yuan, Zeng, Yi, Si, Hai-Bo, Xie, Hui-Qi, Shen, Bin. 2022. Exosomes Derived From Human Urine-Derived Stem Cells Overexpressing miR-140-5p Alleviate Knee Osteoarthritis Through Downregulation of VEGFA in a Rat Model. In The American journal of sports medicine, 50, 1088-1105. doi:10.1177/03635465221073991. https://pubmed.ncbi.nlm.nih.gov/35179989/

4. Tanaka-Watanabe, Yoko, Asahara, Hiroshi. . [Joint and microRNA]. In Nihon Rinsho Men'eki Gakkai kaishi = Japanese journal of clinical immunology, 35, 447-54. doi:. https://pubmed.ncbi.nlm.nih.gov/23291479/

5. Shvedova, Maria, Kobayashi, Tatsuya. 2020. MicroRNAs in cartilage development and dysplasia. In Bone, 140, 115564. doi:10.1016/j.bone.2020.115564. https://pubmed.ncbi.nlm.nih.gov/32745689/

6. Liang, Yujie, Xu, Xiao, Li, Xingfu, Wang, Daping, Xia, Jiang. 2020. Chondrocyte-Targeted MicroRNA Delivery by Engineered Exosomes toward a Cell-Free Osteoarthritis Therapy. In ACS applied materials & interfaces, 12, 36938-36947. doi:10.1021/acsami.0c10458. https://pubmed.ncbi.nlm.nih.gov/32814390/