Scx, also known as Scleraxis, is a transcription factor that plays a crucial role in the development and maintenance of tendon and ligament tissues. It is essential for the differentiation of tendon-and ligament-forming cells, and is involved in regulating the extracellular matrix (ECM) composition in these tissues [1,2,3,4,5,6].

In a study using a Scx-CreERT2 mouse line, Scx lineage cells were found to differentiate into a subset of chondrocytes in the temporomandibular joint, contributing to joint growth and maintenance [2]. In another study, Scx-GFP transgenic rats were used to monitor Scx expression. It was observed that Scx+/Sox9+ cells, which were most abundant in 3-week-old rats near the rotator cuff tendon-to-bone attachment site, may function in rotator cuff repair [3]. Additionally, deletion of suppressor of fused (Sufu) in cathepsin K-Cre-expressing cells (which label a subpopulation of Scx+ tendon-derived progenitor cells) led to spontaneous and progressive ligament, tendon, and periarticular ossification, suggesting a role of Scx+ cells in heterotopic ossification [5].

In conclusion, Scx is vital for tendon, ligament, and related connective tissue development and repair. Studies using gene-targeted mouse and rat models, such as Scx-CreERT2 mice and Scx-GFP transgenic rats, have revealed its role in processes like joint growth, rotator cuff repair, and heterotopic ossification. These findings contribute to our understanding of connective tissue-related diseases and potential therapeutic strategies [2,3,5].

References:

1. Grinstein, Mor, Tsai, Stephanie L, Montoro, Daniel, Rajagopal, Jayaraj, Galloway, Jenna L. 2024. A latent Axin2+/Scx+ progenitor pool is the central organizer of tendon healing. In NPJ Regenerative medicine, 9, 30. doi:10.1038/s41536-024-00370-2. https://pubmed.ncbi.nlm.nih.gov/39420021/

2. Ma, Chi, Jing, Yan, Li, Hui, Huang, Alice, Feng, Jian. 2020. ScxLin cells directly form a subset of chondrocytes in temporomandibular joint that are sharply increased in Dmp1-null mice. In Bone, 142, 115687. doi:10.1016/j.bone.2020.115687. https://pubmed.ncbi.nlm.nih.gov/33059101/

3. Fukuma, Yuko, Tokunaga, Takuya, Tanimura, Shuntaro, Karasugi, Tatsuki, Miyamoto, Takeshi. 2023. Potential function of Scx+/Sox9+ cells as progenitor cells in rotator cuff tear repair in rats. In Biochemical and biophysical research communications, 676, 84-90. doi:10.1016/j.bbrc.2023.07.039. https://pubmed.ncbi.nlm.nih.gov/37499368/

4. Sugimoto, Yuki, Takimoto, Aki, Akiyama, Haruhiko, Hiraki, Yuji, Shukunami, Chisa. 2013. Scx+/Sox9+ progenitors contribute to the establishment of the junction between cartilage and tendon/ligament. In Development (Cambridge, England), 140, 2280-8. doi:10.1242/dev.096354. https://pubmed.ncbi.nlm.nih.gov/23615282/

5. Feng, Heng, Xing, Wenhui, Han, Yujiao, Bi, Qing, Zou, Weiguo. . Tendon-derived cathepsin K-expressing progenitor cells activate Hedgehog signaling to drive heterotopic ossification. In The Journal of clinical investigation, 130, 6354-6365. doi:10.1172/JCI132518. https://pubmed.ncbi.nlm.nih.gov/32853181/

6. Ideo, Katsumasa, Tokunaga, Takuya, Shukunami, Chisa, Hiraki, Yuji, Miyamoto, Takeshi. 2020. Role of Scx+/Sox9+ cells as potential progenitor cells for postnatal supraspinatus enthesis formation and healing after injury in mice. In PloS one, 15, e0242286. doi:10.1371/journal.pone.0242286. https://pubmed.ncbi.nlm.nih.gov/33259516/