Inflammatory Crosstalk Between Rotator Cuff Tissues is Altered with Age and Sex

Area of Science:

• Musculoskeletal biology
• Tissue engineering
• Aging research

Background:

• Musculoskeletal disorders, especially shoulder issues, are prevalent in aging populations.
• Initiating factors of joint degeneration are poorly understood, with limited focus on inter-tissue communication.
• Local interactions within the shoulder joint, specifically bone-tendon-muscle (BTM) crosstalk, remain underexplored.

Purpose of the Study:

• To investigate age- and sex-related differences in bone-tendon-muscle (BTM) crosstalk within the shoulder.
• To test the hypothesis that BTM interactions vary by age and sex, with older/female tissues showing reduced secretory activity.

Main Methods:

• Utilized novel in vitro monocultures and co-cultures of explanted whole shoulder tissues from young and aged C57BL/6J mice.
• Assessed inflammatory responses, including cytokine secretion, across bone, tendon, and muscle tissues.
• Examined differences in tissue interactions based on age and sex.

Main Results:

• Demonstrated significant age- and sex-dependent differences in cytokine secretion, with aged mice exhibiting altered inflammatory profiles.
• Observed increased pro-inflammatory cytokine secretion in monocultures, amplified by aging.
• Found bone-tendon crosstalk mediated by secreted factors, while muscle-tendon communication required physical contact; aging disrupted this crosstalk, diminishing sex differences.

Conclusions:

• Tendon plays a critical role in mediating shoulder inter-tissue communication, which is disrupted by aging.
• Age-related decline in tissue-specific signaling appears to override sex-based distinctions in communication patterns.
• Findings highlight the complex interplay of age and sex in musculoskeletal health and degeneration.