Abstract
Background: Anterior cruciate ligament (ACL) tears result in significant quadriceps muscle atrophy that is resistant to recovery despite extensive rehabilitation. Recent work suggests an elevated fibrotic burden in the quadriceps muscle after the injury, which may limit recovery. Elucidating the mechanisms and cell types involved in the progression of fibrosis is critical for developing new treatment strategies. Purpose: To identify factors contributing to the elevated fibrotic burden found after the injury. Study Design: Descriptive laboratory study. Methods: After an ACL injury, muscle biopsy specimens were obtained from the injured and noninjured vastus lateralis of young adults (n = 14, mean ± SD: 23 ± 4 years). The expression of myostatin, transforming growth factor β, and other regulatory factors was measured, and immunohistochemical analyses were performed to assess turnover of extracellular matrix components. Results: Injured limb skeletal muscle demonstrated elevated myostatin gene (P <.005) and protein (P <.0005) expression, which correlated (R 2 = 0.38, P <.05) with fibroblast cell abundance. Immunohistochemical analysis showed that human fibroblasts express the activin type IIB receptor and that isolated primary human muscle-derived fibroblasts increased proliferation after myostatin treatment in vitro (P <.05). Collagen 1 and fibronectin, primary components of the muscle extracellular matrix, were significantly higher in the injured limb (P <.05). The abundance of procollagen 1–expressing cells as well as a novel index of collagen remodeling was also elevated in the injured limb (P <.05). Conclusion: These findings support a role for myostatin in promoting fibrogenic alterations within skeletal muscle after an ACL injury. Clinical Relevance: The current work shows that the cause of muscle quality decline after ACL injury likely involves elevated myostatin expression, and future studies should explore therapeutic inhibition of myostatin to facilitate improvements in muscle recovery and return to sport.
| Original language | English (US) |
|---|---|
| Journal | American Journal of Sports Medicine |
| DOIs | |
| State | Published - Jan 1 2019 |
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Keywords
- collagen
- extracellular matrix
- fibroblast
- quadriceps
ASJC Scopus subject areas
- Orthopedics and Sports Medicine
- Physical Therapy, Sports Therapy and Rehabilitation
Cite this
Anterior Cruciate Ligament Tear Promotes Skeletal Muscle Myostatin Expression, Fibrogenic Cell Expansion, and a Decline in Muscle Quality. / Peck, Bailey D.; Brightwell, Camille R.; Johnson, Darren L.; Ireland, Mary Lloyd; Noehren, Brian; Fry, Christopher.
In: American Journal of Sports Medicine, 01.01.2019.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Anterior Cruciate Ligament Tear Promotes Skeletal Muscle Myostatin Expression, Fibrogenic Cell Expansion, and a Decline in Muscle Quality
AU - Peck, Bailey D.
AU - Brightwell, Camille R.
AU - Johnson, Darren L.
AU - Ireland, Mary Lloyd
AU - Noehren, Brian
AU - Fry, Christopher
PY - 2019/1/1
Y1 - 2019/1/1
N2 - Background: Anterior cruciate ligament (ACL) tears result in significant quadriceps muscle atrophy that is resistant to recovery despite extensive rehabilitation. Recent work suggests an elevated fibrotic burden in the quadriceps muscle after the injury, which may limit recovery. Elucidating the mechanisms and cell types involved in the progression of fibrosis is critical for developing new treatment strategies. Purpose: To identify factors contributing to the elevated fibrotic burden found after the injury. Study Design: Descriptive laboratory study. Methods: After an ACL injury, muscle biopsy specimens were obtained from the injured and noninjured vastus lateralis of young adults (n = 14, mean ± SD: 23 ± 4 years). The expression of myostatin, transforming growth factor β, and other regulatory factors was measured, and immunohistochemical analyses were performed to assess turnover of extracellular matrix components. Results: Injured limb skeletal muscle demonstrated elevated myostatin gene (P <.005) and protein (P <.0005) expression, which correlated (R 2 = 0.38, P <.05) with fibroblast cell abundance. Immunohistochemical analysis showed that human fibroblasts express the activin type IIB receptor and that isolated primary human muscle-derived fibroblasts increased proliferation after myostatin treatment in vitro (P <.05). Collagen 1 and fibronectin, primary components of the muscle extracellular matrix, were significantly higher in the injured limb (P <.05). The abundance of procollagen 1–expressing cells as well as a novel index of collagen remodeling was also elevated in the injured limb (P <.05). Conclusion: These findings support a role for myostatin in promoting fibrogenic alterations within skeletal muscle after an ACL injury. Clinical Relevance: The current work shows that the cause of muscle quality decline after ACL injury likely involves elevated myostatin expression, and future studies should explore therapeutic inhibition of myostatin to facilitate improvements in muscle recovery and return to sport.
AB - Background: Anterior cruciate ligament (ACL) tears result in significant quadriceps muscle atrophy that is resistant to recovery despite extensive rehabilitation. Recent work suggests an elevated fibrotic burden in the quadriceps muscle after the injury, which may limit recovery. Elucidating the mechanisms and cell types involved in the progression of fibrosis is critical for developing new treatment strategies. Purpose: To identify factors contributing to the elevated fibrotic burden found after the injury. Study Design: Descriptive laboratory study. Methods: After an ACL injury, muscle biopsy specimens were obtained from the injured and noninjured vastus lateralis of young adults (n = 14, mean ± SD: 23 ± 4 years). The expression of myostatin, transforming growth factor β, and other regulatory factors was measured, and immunohistochemical analyses were performed to assess turnover of extracellular matrix components. Results: Injured limb skeletal muscle demonstrated elevated myostatin gene (P <.005) and protein (P <.0005) expression, which correlated (R 2 = 0.38, P <.05) with fibroblast cell abundance. Immunohistochemical analysis showed that human fibroblasts express the activin type IIB receptor and that isolated primary human muscle-derived fibroblasts increased proliferation after myostatin treatment in vitro (P <.05). Collagen 1 and fibronectin, primary components of the muscle extracellular matrix, were significantly higher in the injured limb (P <.05). The abundance of procollagen 1–expressing cells as well as a novel index of collagen remodeling was also elevated in the injured limb (P <.05). Conclusion: These findings support a role for myostatin in promoting fibrogenic alterations within skeletal muscle after an ACL injury. Clinical Relevance: The current work shows that the cause of muscle quality decline after ACL injury likely involves elevated myostatin expression, and future studies should explore therapeutic inhibition of myostatin to facilitate improvements in muscle recovery and return to sport.
KW - collagen
KW - extracellular matrix
KW - fibroblast
KW - quadriceps
UR - http://www.scopus.com/inward/record.url?scp=85064639685&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85064639685&partnerID=8YFLogxK
U2 - 10.1177/0363546519832864
DO - 10.1177/0363546519832864
M3 - Article
JO - American Journal of Sports Medicine
JF - American Journal of Sports Medicine
SN - 0363-5465
ER -