Abstract
We examined the relationship between grip strength declines and muscle-tendon responses induced by long-term performance of a high-repetition, low-force (HRLF) reaching task in rats. We hypothesized that grip strength declines would correlate with inflammation, fibrosis and degradation in flexor digitorum muscles and tendons. Grip strength declined after training, and further in weeks 18 and 24, in reach limbs of HRLF rats. Flexor digitorum tissues of reach limbs showed low-grade increases in inflammatory cytokines: IL-1β after training and in week 18, IL-1α in week 18, TNF-α and IL-6 after training and in week 24, and IL-10 in week 24, with greater increases in tendons than muscles. Similar cytokine increases were detected in serum with HRLF: IL-1α and IL-10 in week 18, and TNF-α and IL-6 in week 24. Grip strength correlated inversely with IL-6 in muscles, tendons and serum, and TNF-α in muscles and serum. Four fibrogenic proteins, TGFB1, CTGF, PDGFab and PDGFbb, and hydroxyproline, a marker of collagen synthesis, increased in serum in HRLF weeks 18 or 24, concomitant with epitendon thickening, increased muscle and tendon TGFB1 and CTGF. A collagenolytic gelatinase, MMP2, increased by week 18 in serum, tendons and muscles of HRLF rats. Grip strength correlated inversely with TGFB1 in muscles, tendons and serum; with CTGF-immunoreactive fibroblasts in tendons; and with MMP2 in tendons and serum. Thus, motor declines correlated with low-grade systemic and musculotendinous inflammation throughout task performance, and increased fibrogenic and degradative proteins with prolonged task performance. Serum TNF-α, IL-6, TGFB1, CTGF and MMP2 may serve as serum biomarkers of work-related musculoskeletal disorders, although further studies in humans are needed.
Highlights
According to the Bureau of Labor Statistics report entitled Nonfatal Occupational Injuries and Illnesses Requiring Days Away from Work, 2011, musculoskeletal disorders accounted for 33 percent of all lost work time workplace injuries and illnesses in the U.S and required a median of 11 days away from work [1]
No differences were found between normal control (NC) and food restricted (FRC) rats; data from both groups were combined into a single control (C) group
Since we have previously shown that grip strength declines correlate with increased muscle and tendon cytokines in rats performing a similar task for 8 weeks [44], we examined flexor digitorum muscles and tendons, bilaterally, for inflammatory cytokines using ELISA (Fig. 3)
Summary
According to the Bureau of Labor Statistics report entitled Nonfatal Occupational Injuries and Illnesses Requiring Days Away from Work, 2011, musculoskeletal disorders accounted for 33 percent of all lost work time workplace injuries and illnesses in the U.S and required a median of 11 days away from work [1]. A small number of studies have searched for and detected serum biomarkers of inflammation in patients with upper extremity musculoskeletal disorders of short duration (,3 months), including C-reactive protein, interleukin- 6 (IL-6), tumor necrosis factor-alpha (TNF-a), and members of the IL-1 family [2,3,4] The results of these studies suggest a role for inflammatory cytokines early in the course of upper extremity MSDs. tissues collected from patients with upper extremity MSDs at the time of surgical intervention show increased IL-1b immunoreactive fibroblasts and IL-6 (which can be pro- or anti-inflammatory depending on accompanying cytokines) [11,12,13], but few acute inflammatory responses [7,11]. IL-6, IL-1b and TNF-a have been deemed as pro-fibrotic cytokines due to their mitogenic and chemotactic effects on fibroblasts and induction of fibrogenic proteins [14,15,16,17,18,19]
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