Role of myostatin (GDF-8) signaling in the human anterior cruciate ligament

Sadanand T Fulzele, Phonepasong Arounleut, Matthew Cain, Samuel Herberg, David M Hunter, Karl Wenger, Mark W Hamrick

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

Myostatin, also referred to as growth and differentiation factor-8 (GDF-8), is expressed in muscle tissue where it functions to suppress myoblast proliferation and myofiber hypertrophy. Recently, myostatin and its receptor, the type IIB activin receptor (ActRIIB), were detected in the leg tendons of mice, and recombinant myostatin was shown to increase cellular proliferation and the expression of type 1 collagen in primary fibroblasts from mouse tendons. We sought to determine whether myostatin and its receptor were present in human anterior cruciate ligament (ACL) tissue, and if myostatin treatment had any effect on primary ACL fibroblasts. ACL tissue samples were obtained from material discarded during ACL reconstruction surgery. Real-time PCR and immunohistochemistry demonstrate that both myostatin and its receptor are abundant in the human ACL. Primary fibroblasts isolated from human ACL specimens were treated with recombinant myostatin, and myostatin treatment increased fibroblast proliferation as well as the expression of tenascin C (TNC), type 1 collagen, and transforming growth factor-b1. Real-time PCR analysis of TNC and type 1 collagen expression in ACL specimens from normal mice and mice lacking myostatin supported these findings by showing that both TNC and type 1 collagen were downregulated in ACL tissue from myostatin-deficient mice. Together, these data suggest that myostatin is a pro-fibrogenic factor that enhances cellular proliferation and extracellular matrix synthesis byACLfibroblasts. Recombinant myostatin maytherefore have therapeutic applications in the area of tendon and ligament engineering and regeneration.

Original languageEnglish (US)
Pages (from-to)1113-1118
Number of pages6
JournalJournal of Orthopaedic Research
Volume28
Issue number8
DOIs
StatePublished - Aug 1 2010

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Keywords

  • Growth and differentiation factors
  • Knee ligaments
  • TGF-β1
  • Tenascin C

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine

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