Potential function of Scx+/Sox9+cells as progenitor cells in rotator cuff tear repair in rats

Tendons and their attachment sites to bone, fibrocartilaginous tissues, have poor self-repair capacity when they rupture, and have risks of retear even after surgical repair. Thus, defining mechanisms underlying their repair is required in order to stimulate tendon repairing capacity. Here we used a rat surgical rotator cuff tear repair model and identified cells expressing the transcription factors Scleraxis (Scx) and SRY-box 9 (Sox9) as playing a crucial role in rotator cuff tendon-to-bone repair. Given the challenges of establishing stably reproducible models of surgical rotator cuff tear repair in mice, we newly established Scx-GFP transgenic rats in which Scx expression can be monitored by GFP. We observed tissue-specific GFP expression along tendons in developing ScxGFP transgenic rats and were able to successfully monitor tissue-specific Scx expression based on GFP signals. Among 3-, 6-, and 12-week-old ScxGFP rats, Scx+/Sox9+ cells were most abundant in 3-week-old rats near the site of humerus bone attachment to the rotator cuff tendon, while we observed significantly fewer cells in the same area in 6-or 12-week-old rats. We then applied a rotator cuff repair model using ScxGFP rats and observed the largest number of Scx+/Sox9+ cells at postoperative repair sites of 3-week-old relative to 6-or 12-week-old rats. Tendons attach to bone via fibrocartilaginous tissue, and cartilage-like tissue was seen at repair sites of 3 -weekold but not 6-or 12-week-old rats during postoperative evaluation. Our findings suggest that Scx+/Sox9+ cells may function in rotator cuff repair, and that ScxGFP rats could serve as useful tools to develop therapies to promote rotator cuff repair by enabling analysis of these activities.

Automated summary

Using Scx-GFP transgenic rats, this study identified cells expressing Sceraxis (Scx) and SRY-box 9 (Sox9) as crucial for rotator cuff tendon-to-bone repair. The highest number of Scx+/Sox9+ cells was found in 3-week-old rats during the repair process, while significantly fewer cells were observed in 6- or 12-week-old rats. Additionally, cartilage-like tissue was only seen at repair sites of 3-week-old rats. These findings suggest the potential role of Scx+/Sox9+ cells in rotator cuff repair and the usefulness of Scx-GFP rats for developing therapeutic strategies.