Role of myostatin (GDF-8) signaling in the human anterior cruciate ligament.
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-beta1. 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 by ACL fibroblasts. Recombinant myostatin may therefore have therapeutic applications in the area of tendon and ligament engineering and regeneration.
Fulzele
Sadanand
S
Department of Orthopaedic Surgery & Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, Georgia 30912, USA.
Arounleut
Phonepasong
P
Cain
Matthew
M
Herberg
Samuel
S
Hunter
Monte
M
Wenger
Karl
K
Hamrick
Mark W
MW
D030301:Activin Receptors, Type II / Q000096:biosynthesis; D000293:Adolescent; D000328:Adult; D000818:Animals; D016118:Anterior Cruciate Ligament / Q000166:cytology / Q000378:metabolism*; D049109:Cell Proliferation; D024042:Collagen Type I / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D008297:Male; D051379:Mice; D055435:Myostatin / Q000172:deficiency / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D019063:Tenascin / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
D024042:Collagen Type I; C525911:MSTN protein, human; C525912:Mstn protein, mouse; D055435:Myostatin; D019063:Tenascin; D053773:Transforming Growth Factor beta1; D030301:Activin Receptors, Type II; C425584:activin receptor type II-B