Blocking CTGF/CCN2 reduces established skeletal muscle fibrosis in a rat model of overuse injury Article Swipe
Mary F. Barbe
,
Brendan Hilliard
,
Mamta Amin
,
Michele Y. Harris
,
Lucas J. Hobson
,
Geneva E. Cruz
,
Steven N. Popoff
·
YOU?
·
· 2020
· Open Access
·
· DOI: https://doi.org/10.1096/fj.202000240rr
YOU?
·
· 2020
· Open Access
·
· DOI: https://doi.org/10.1096/fj.202000240rr
Tissue fibrosis is a hallmark of overuse musculoskeletal injuries and contributes to functional declines. We tested whether inhibition of CCN2 (cellular communication network factor 2, previously known as connective tissue growth factor, CTGF) using a specific antibody (termed FG‐3019 or pamrevlumab) reduces established overuse‐induced muscle fibrosis in a clinically relevant rodent model of upper extremity overuse injury. Young adult rats performed a high repetition high force (HRHF) reaching and lever‐pulling task for 18 weeks, after first being shaped for 6 weeks to learn this operant task. Rats were then euthanized (HRHF‐Untreated), or rested and treated for 6 weeks with FG‐3019 (HRHF‐Rest/FG‐3019) or a human IgG as a vehicle control (HRHF‐Rest/IgG). HRHF‐Untreated and HRHF‐Rest/IgG rats had higher muscle levels of several fibrosis‐related proteins (TGFβ1, CCN2, collagen types I and III, and FGF2), and higher muscle numbers of alpha SMA and pERK immunopositive cells, compared to control rats. Each of these fibrogenic changes was restored to control levels by the blocking of CCN2 signaling in HRHF‐Rest/FG‐3019 rats, as were HRHF task‐induced increases in serum CCN2 and pro‐collagen I intact N‐terminal protein. Levels of cleaved CCN3, an antifibrotic protein, were lowered in HRHF‐Untreated and HRHF‐Rest/IgG rats, compared to control rats, yet elevated back to control levels in HRHF‐Rest/FG‐3019 rats. Significant grip strength declines observed in HRHF‐Untreated and HRHF‐Rest/IgG rats, were restored to control levels in HRHF‐Rest/FG‐3019 rats. These results are highly encouraging for use of FG‐3019 for therapeutic treatment of persistent skeletal muscle fibrosis, such as those induced with chronic overuse.
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Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1096/fj.202000240rr
- OA Status
- green
- Cited By
- 48
- References
- 68
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W3013244206
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W3013244206Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1096/fj.202000240rrDigital Object Identifier
- Title
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Blocking CTGF/CCN2 reduces established skeletal muscle fibrosis in a rat model of overuse injuryWork title
- Type
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articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
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2020Year of publication
- Publication date
-
2020-03-29Full publication date if available
- Authors
-
Mary F. Barbe, Brendan Hilliard, Mamta Amin, Michele Y. Harris, Lucas J. Hobson, Geneva E. Cruz, Steven N. PopoffList of authors in order
- Landing page
-
https://doi.org/10.1096/fj.202000240rrPublisher landing page
- Open access
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YesWhether a free full text is available
- OA status
-
greenOpen access status per OpenAlex
- OA URL
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https://www.ncbi.nlm.nih.gov/pmc/articles/7200299Direct OA link when available
- Concepts
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CTGF, Fibrosis, Connective tissue, Endocrinology, Rest (music), Internal medicine, Medicine, Growth factor, Pathology, ReceptorTop concepts (fields/topics) attached by OpenAlex
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48Total citation count in OpenAlex
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2025: 4, 2024: 4, 2023: 6, 2022: 14, 2021: 12Per-year citation counts (last 5 years)
- References (count)
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68Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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