Growth and repair factors, osteoactivin, matrix metalloproteinase and heat shock protein 72, increase with resolution of inflammation in musculotendinous tissues in a rat model of repetitive grasping

BMC Musculoskelet Disord. 2016 Jan 18;17:34. doi: 10.1186/s12891-016-0892-3.


Background: Expression of the growth factor osteoactivin (OA) increases during tissue degeneration and regeneration, fracture repair and after denervation-induced disuse atrophy, concomitant with increased matrix metalloproteinases (MMPs). However, OA's expression with repetitive overuse injuries is unknown. The aim of this study was to evaluate: 1) OA expression in an operant rat model of repetitive overuse; 2) expression of MMPs; 3) inflammatory cytokines indicative of injury or inflammation; and 4) the inducible form of heat shock protein 70 (HSPA1A/HSP72) as the latter is known to increase during metabolic stress and to be involved in cellular repair. Young adult female rats performed a high repetition negligible force (HRNF) food retrieval task for up to 6 weeks and were compared to control rats.

Methods: Flexor digitorum muscles and tendons were collected from 22 young adult female rats performing a HRNF reaching task for 3 to 6 weeks, and 12 food restricted control (FRC) rats. OA mRNA levels were assessed by quantitative polymerase chain reaction (qPCR). OA, MMP-1, -2, -3, and -13 and HSP72 protein expression was assayed using Western blotting. Immunohistochemistry and image analysis was used to evaluate OA and HSP72 expression. ELISA was performed for HSP72 and inflammatory cytokines.

Results: Flexor digitorum muscles and tendons from 6-week HRNF rats showed increased OA mRNA and protein expression compared to FRC rats. MMP-1, -2 and -3 progressively increased in muscles whereas MMP-1 and -3 increased in tendons with HRNF task performance. HSP72 increased in 6-week HRNF muscles and tendons, compared to controls, and co-localized with OA in the myofiber sarcolemma. IL-1alpha and beta increased transiently in tendons or muscles in HRNF week 3 before resolving in week 6.

Conclusion: The simultaneous increases of OA with factors involved in tissue repair (MMPs and HSP72) supports a role of OA in tissue regeneration after repetitive overuse.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cumulative Trauma Disorders / metabolism*
  • Cumulative Trauma Disorders / prevention & control
  • Disease Models, Animal
  • Female
  • HSP72 Heat-Shock Proteins / biosynthesis*
  • Hand Strength / physiology
  • Inflammation / metabolism
  • Inflammation / prevention & control
  • Intercellular Signaling Peptides and Proteins / biosynthesis
  • Matrix Metalloproteinases / biosynthesis*
  • Membrane Glycoproteins / biosynthesis*
  • Muscle, Skeletal / metabolism*
  • Muscle, Skeletal / pathology
  • Rats
  • Rats, Sprague-Dawley
  • Tendons / metabolism*
  • Tendons / pathology


  • Gpnmb protein, rat
  • HSP72 Heat-Shock Proteins
  • Intercellular Signaling Peptides and Proteins
  • Membrane Glycoproteins
  • Matrix Metalloproteinases