Tnmd, also known as tenomodulin, is a type II transmembrane glycoprotein encoding gene mapped to the X chromosome. It plays a crucial role in regulating tendon growth, acts as an efficient marker of tenocyte differentiation, and is involved in tenocyte proliferation, tendon development, and angiogenesis inhibition. It also participates in processes like cell adhesion, cell morphology determination, cell aging, and bone mineral density regulation [4].

A case-control study of 356 Han Chinese pregnant women found that the polymorphism of TNMD rs4828038 might be associated with the risk of late-onset preeclampsia, suggesting it could be a target site for genetic diagnosis and therapy [1]. In a rat model of rotator cuff rupture, secretome-hMSCs treatment improved tendon repair by upregulating TNMD expression [2]. Gene transfection of Tnmd in rat bone tissue regeneration inhibited bone formation, with the effect depending on the non-viral gene transfection vector [3]. Single-cell RNA sequencing of arrhythmogenic right ventricular cardiomyopathy (ARVC) patients showed that the right ventricle was enriched with TNMD+ fibroblasts [5]. In in vitro angiogenesis studies, TNMD had a stronger inhibitory effect on tube formation than ranibizumab [6]. Also, activation of Wnt/β-catenin signaling suppressed Tnmd expression in rat tendon-derived cells [7], while stretch-induced Tnmd expression promoted tenocyte migration via F-actin and chromatin remodeling [8].

In summary, Tnmd is essential for tendon-related functions, angiogenesis regulation, and may be involved in diseases such as preeclampsia and ARVC. Studies using animal models and in vitro experiments have revealed its role in various biological processes, providing insights into potential therapeutic targets and mechanisms for related diseases.

References:

1. Song, Wei, Wang, He, Ma, Lingyu, Chen, Ying. 2022. Associations between the TNMD rs4828038 and ACE2 rs879922 polymorphisms and preeclampsia susceptibility: a case-control study. In Journal of obstetrics and gynaecology : the journal of the Institute of Obstetrics and Gynaecology, 42, 1132-1136. doi:10.1080/01443615.2021.2012438. https://pubmed.ncbi.nlm.nih.gov/34996340/

2. Fredianto, Meiky, Herman, Herry, Ismiarto, Yoyos Dias, Putra, Agung, Hidayah, Nurul. . Combination Effect of Rotator Cuff Repair with Secretome-hypoxia MSCs Ameliorates TNMD, RUNX2, and Healing Histology Score in Rotator Cuff Tear Rats. In The archives of bone and joint surgery, 11, 617-624. doi:10.22038/ABJS.2023.67933.3218. https://pubmed.ncbi.nlm.nih.gov/37873528/

3. Wang, Han, Tenkumo, Taichi, Nemoto, Eiji, Ogawa, Toru, Sasaki, Keiichi. 2023. Introduction of tenomodulin by gene transfection vectors for rat bone tissue regeneration. In Regenerative therapy, 22, 99-108. doi:10.1016/j.reth.2022.12.008. https://pubmed.ncbi.nlm.nih.gov/36712960/

4. Alexandrov, Vesselin P, Naimov, Samir I. . A Prospectus of Tenomodulin. In Folia medica, 58, 19-27. doi:10.1515/folmed-2016-0003. https://pubmed.ncbi.nlm.nih.gov/27383874/

5. Fu, Mengxia, Hua, Xiumeng, Shu, Songren, Hu, Shengshou, Song, Jiangping. 2024. Single-cell RNA sequencing in donor and end-stage heart failure patients identifies NLRP3 as a therapeutic target for arrhythmogenic right ventricular cardiomyopathy. In BMC medicine, 22, 11. doi:10.1186/s12916-023-03232-8. https://pubmed.ncbi.nlm.nih.gov/38185631/

6. Wang, Wei, Liu, Guang-Xu, Li, Yue-Hua, Li, Xue-Dong, He, Yan. 2017. Inhibitory effect of tenomodulin versus ranibizumab on in vitro angiogenesis. In International journal of ophthalmology, 10, 1212-1216. doi:10.18240/ijo.2017.08.04. https://pubmed.ncbi.nlm.nih.gov/28861344/

7. Kishimoto, Yasuzumi, Ohkawara, Bisei, Sakai, Tadahiro, Docheva, Denitsa, Ohno, Kinji. 2017. Wnt/β-catenin signaling suppresses expressions of Scx, Mkx, and Tnmd in tendon-derived cells. In PloS one, 12, e0182051. doi:10.1371/journal.pone.0182051. https://pubmed.ncbi.nlm.nih.gov/28750046/

8. Xu, Pu, Deng, Bin, Zhang, Bingyu, Luo, Qing, Song, Guanbin. 2021. Stretch-Induced Tenomodulin Expression Promotes Tenocyte Migration via F-Actin and Chromatin Remodeling. In International journal of molecular sciences, 22, . doi:10.3390/ijms22094928. https://pubmed.ncbi.nlm.nih.gov/34066472/