Increased levels of apoptosis and p53 in partial-thickness supraspinatus tendon tears
Lundgree K., Lian O., Scott A., Engebresten L. Knee Surg. Sports Traumatol Arthrosc. 2012;
Apoptosis is a type of cell death that regulates tissue healing and cell density. Excessive apoptosis is associated with several degenerative pathologies including tendinopathy. However, the mechanisms of degeneration and the role of apoptosis in the progression of rotator cuff tendinopathy are not well understood. Understanding the degenerative pathway in tendinopathy could lead to better care and new therapeutic interventions. Therefore, the purpose of this study was to quantify apoptosis and explore the role of a key cell death pathway in partially torn supraspinatus tendons. Patients were excluded from this study if they had any factors that would influence the occurrence of apoptosis (i.e., diabetes, systemic inflammatory diseases, nicotine usage). Nine patients (5 men, 4 women; mean age of 54 years) with partial-thickness supraspinatus tendon tears were included. The tears affected at least 50% of the tendon and the shoulders had no subscapularis pathology on magnetic resonance imaging or arthroscopy. During a procedure to arthroscopically repair the tear the investigators harvested biopsies from the edges of the torn supraspinatus and from their intact subscapularis tendon (matched tendon). The study also included 10 control patients (5 men, 5 women: mean age of 44 year) who underwent a labral repair and had no rotator cuff pathology. Among these patients the investigators collected samples of the healthy subscapularis tendon during surgery. All tissue samples were processed and evaluated for tendon degeneration as well as tenocyte density, proliferation, apoptosis, and expression of a key protein involved in regulating cell death. Biopsies revealed that partially torn supraspinatus tendons contained degeneration near the tear and further away from the tear compared to the subscapularis tendon from the same shoulder and healthy subscapularis tendons from control patients. There were also increases in tenocyte density and proliferation within the partially torn supraspinatus tendons compared to the healthy subscapularis tendons. There were no differences in tenocyte density and proliferation within the matched subscapularis tendons compared to the healthy subscapularis tendons. The number of cells undergoing apoptosis was elevated in partial supraspinatus tendons compared to both matched and healthy subscapularis tendons. Additionally, the amount of protein expression related to cell death was higher in the damaged supraspinatus and matched subscapularis tendons compared to the healthy subscapularis tendons.
The progressive nature of a rotator cuff tendinopathy is one of the reasons why this injury has a poor healing capacity. In this study, researchers found that partially-torn supraspinatus tendons had elevated levels of degeneration, tenocyte proliferation, and apoptosis. The elevated levels of cell proliferation and density are what you would expect to find in healing tissue. However, they also found higher levels of apoptosis in not just the partially-torn supraspinatus but also the subscapularis tendons, which may indicate an early role of apoptosis in rotator cuff tendinopathy. This is one of the first studies that found that cell proliferation is accompanied by apoptosis. Increased apoptosis may be involved in on going repair process. One major limitation of this study is that they compared an injured mean age group of 54 years to a reference group with a mean age of 44 years, where usually an older tissue will have more degeneration than a younger tissue. This finding of apoptosis in the early stages of tissue regeneration could represent a possible target for a therapeutic intervention. Do you think that we will have a therapeutic agent that will minimize degeneration with rotator cuff tendinopathy?
Written by: Jane McDevitt, MS, ATC, CSCS
Reviewed: Jeffrey Driban
Related Post:Lundgreen K, Lian O, Scott A, & Engebretsen L (2012). Increased levels of apoptosis and p53 in partial-thickness supraspinatus tendon tears. Knee Surgery, Sports Traumatology, Arthroscopy PMID: 23052118