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 language | English (US) |
|---|---|
| Pages (from-to) | 1113-1118 |
| Number of pages | 6 |
| Journal | Journal of Orthopaedic Research |
| Volume | 28 |
| Issue number | 8 |
| DOIs | |
| State | Published - 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
Cite this
Role of myostatin (GDF-8) signaling in the human anterior cruciate ligament. / Fulzele, Sadanand T; Arounleut, Phonepasong; Cain, Matthew; Herberg, Samuel; Hunter, David M; Wenger, Karl; Hamrick, Mark W.
In: Journal of Orthopaedic Research, Vol. 28, No. 8, 01.08.2010, p. 1113-1118.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Role of myostatin (GDF-8) signaling in the human anterior cruciate ligament
AU - Fulzele, Sadanand T
AU - Arounleut, Phonepasong
AU - Cain, Matthew
AU - Herberg, Samuel
AU - Hunter, David M
AU - Wenger, Karl
AU - Hamrick, Mark W
PY - 2010/8/1
Y1 - 2010/8/1
N2 - 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.
AB - 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.
KW - Growth and differentiation factors
KW - Knee ligaments
KW - TGF-β1
KW - Tenascin C
UR - http://www.scopus.com/inward/record.url?scp=77954721456&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77954721456&partnerID=8YFLogxK
U2 - 10.1002/jor.21112
DO - 10.1002/jor.21112
M3 - Article
C2 - 20186835
AN - SCOPUS:77954721456
VL - 28
SP - 1113
EP - 1118
JO - Journal of Orthopaedic Research
JF - Journal of Orthopaedic Research
SN - 0736-0266
IS - 8
ER -