Published 3/4/2026
Aging accelerates rotator cuff muscle degeneration, driving both spontaneous atrophy and the muscle loss that accompanies tendon tears. A new study presented Monday and Tuesday at the AAOS 2026 Annual Meeting investigated how prostaglandin E2 (PGE2), a regulator of muscle regeneration, affects muscular structure and mitochondrial function in aged mice. Researchers used SW033291, a 15-prostaglandin dehydrogenase inhibitor, to prevent PGE2 breakdown and identify potential pathways to mitigate rotator cuff muscle decline.
“I conducted this study because we frequently see elderly patients with large or massive rotator cuff tears whose surgical outcomes are limited not only by the tendon injury itself, but by profound age-related muscle degeneration,” explained Chongyang Wang, MD, the poster’s corresponding author. “I wanted to better understand the biological mechanisms that make aging muscle more vulnerable and to identify a strategy that could restore muscle quality before or after repair.”
For the study, a total of 20 young (five- to six-month-old) and 100 aged (18- to 20-month-old) female C57BL/6J mice were divided into two groups. The first group included young, aged, and aged plus SW033291 subgroups and was used to study sarcopenia; the second group consisted of tear, tear plus repair, and tear plus repair and SW033291 subgroups and was used to examine the outcomes following a rotator cuff tear (RCT). Researchers performed tissue staining, muscle mass assessments, functional assays, and mitochondrial function tests.
Researchers observed rotator cuff muscle degeneration both in natural aging and in mice with RCTs. These conditions together worsened muscle atrophy and fatty infiltration into the muscle, with the aged tear group showing a decrease in muscle mass from a mean and standard deviation of 45.45 ± 4.04 to 25.18 ± 1.82 mg (P < 0.001) and a reduction in fiber cross-sectional area (CSA) from 1,697.3 ± 108.4 to 1,263.0 ± 56.8 μm2 (P < 0.001). This was linked to increased 15-PGDH activity and a reduction in PGE2 levels in the aged tear group (from 2.897 ± 0.177 to 1.873 ± 0.179 ng/g muscle; P < 0.001). SW033291 treatment increased the level of PGE2, reversing muscle atrophy by mitigating mitochondrial dysfunction in both models.
“What surprised us most was the strong correlation between reduced PGE2 levels and worsening mitochondrial dysfunction in aged rotator cuff muscle,” said Dr. Wang. “By inhibiting 15-PGDH and restoring PGE2 to a more youthful level, we were able to significantly improve muscle mass, reduce fatty infiltration, and enhance contractile strength in both natural aging and tear models.”
“The significance of this research lies in shifting the paradigm from focusing solely on tendon repair to biologically optimizing the muscle environment,” Dr. Wang added. “Targeting PGE2 metabolism may represent a novel therapeutic strategy to improve healing and functional outcomes in elderly patients with rotator cuff tears.”
The authors of “PGE2 Ameliorates Aging-Aggravated Rotator Cuff Muscle Atrophy is Effective in Preventing Massive Rotator Cuff Tear in the Elderly” are Chongyang Wang, MD and Haoyuan Wang, MD.
Theresa Witham is the managing editor of AAOS Now.