Murine supraspinatus tendon injury model to identify the cellular origins of rotator cuff healing

Ryu Yoshida,Farhang Alaee,Felix Dyrna,Mark S Kronenberg,Peter Maye,Ivo Kalajzic,David W Rowe,Augustus D Mazzocca,Nathaniel A Dyment

doi:10.1080/03008207.2016.1189910

Ryu Yoshida, Farhang Alaee + Show 7 more

Open Access

https://doi.org/10.1080/03008207.2016.1189910

Copy DOI

Abstract

ABSTRACTPurpose of this study: To elucidate the origin of cell populations that contribute to rotator cuff healing, we developed a mouse surgical model where a full-thickness, central detachment is created in the supraspinatus. Materials and methods: Three different inducible Cre transgenic mice with Ai9-tdTomato reporter expression (PRG4-9, αSMA-9, and AGC-9) were used to label different cell populations in the shoulder. The defect was created surgically in the supraspinatus. The mice were injected with tamoxifen at surgery to label the cells and sacrificed at 1, 2, and 5 weeks postoperatively. Frozen sections were fluorescently imaged then stained with Toluidine Blue and re-imaged. Results: Three notable changes were apparent postoperatively. (1) A long thin layer of tissue formed on the bursal side overlying the supraspinatus tendon. (2) The tendon proximal to the defect initially became hypercellular and disorganized. (3) The distal stump at the insertion underwent minimal remodeling. In the uninjured shoulder, tdTomato expression was seen in the tendon midsubstance and paratenon cell on the bursal side in PRG4-9, in paratenon, blood vessels, and periosteum of acromion in SMA-9, and in articular cartilage, unmineralized fibrocartilage of supraspinatus enthesis, and acromioclavicular joint in AGC-9 mice. In the injured PRG4-9 and SMA-9 mice, the healing tissues contained an abundant number of tdTomato+ cells, while minimal contribution of tdTomato+ cells was seen in AGC-9 mice. Conclusions: The study supports the importance of the bursal side of the tendon to rotator cuff healing and PRG4 and αSMA may be markers for these progenitor cells.

Highlights

Rotator cuff pathology is a common source of shoulder pain, estimated to account for over 4.5 million clinician visits and 250,000 surgeries annually in the United States [1]
TdTomato expression was seen in the tendon midsubstance and paratenon cell on the bursal side in PRG4-9, in paratenon, blood vessels, and periosteum of acromion in SMA-9, and in articular cartilage, unmineralized fibrocartilage of supraspinatus enthesis, and acromioclavicular joint in AGC-9 mice
In the injured PRG4-9 and SMA-9 mice, the healing tissues contained an abundant number of tdTomato+ cells, while minimal contribution of tdTomato+ cells was seen in AGC-9 mice

Summary

Introduction

Rotator cuff pathology is a common source of shoulder pain, estimated to account for over 4.5 million clinician visits and 250,000 surgeries annually in the United States [1]. The burden will likely continue to increase with the aging population, as the incidence and prevalence of rotator cuff ailments increases with age [2]. Despite advances in imaging technology, operative technique, and surgical hardware, rotator cuff injuries are still challenging to treat. Partial-thickness tears are difficult to manage, often do not heal [3], and can progress to full-thickness tears. The appropriate timing and indications for surgical intervention are under debate [4]. Many patients with fullthickness tears that fail conservative management undergo surgical repair, but retears are common, especially with large-sized tears [5,6]

Objectives

Methods

Results

Conclusion