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Repetitive mechanical stretching modulates IL-1β induced COX-2, MMP-1 expression, and PGE2 production in human patellar tendon fibroblasts
Open accessAbstract
While mechanical loading is known to be essential in maintaining tendon homeostasis, repetitive mechanical loading has also been implicated in the etiology of tendon overuse injuries. The purpose of this study was to determine whether cyclic mechanical stretching regulates inflammatory responses induced by interleukin-1beta (IL-1beta) treatment in human patellar tendon fibroblasts (HPTFs). HPTFs were grown in microgrooved silicone dishes, where they became elongated in shape and aligned with the microgrooves, which is similar to the shape and organization of tendon fibroblasts in vivo. Cyclic uniaxial stretching was then applied to silicone culture dishes with a 4% or 8% stretch at a stretching frequency of 0.5 Hz for a duration of 4 h in the presence or absence of 10 pM IL-1beta treatment. Non-stretched cells in the presence or absence of IL-1beta were used for controls, respectively. The expression of cyclooxygenase-2 (COX-2), matrix metalloproteinase-1 (MMP-1), and the production of prostaglandin E2 (PGE2) were measured. In the absence of stretching, it was found that 10 pM of IL-1beta markedly induced higher levels of COX-2, MMP-1 gene expression, and PGE2 production than non-treated cells. Furthermore, cells with 4% stretching decreased the COX-2 and MMP-1 gene expression and PGE2 production that were stimulated by IL-1beta, whereas cells with 8% stretching further increased these gene products and/or expression levels in addition to the effects of IL-1beta stimulation. Thus, the results suggest that repetitive, small-magnitude stretching is anti-inflammatory, whereas large-magnitude stretching is pro-inflammatory. Therefore, moderate exercise may be beneficial to reducing tendon inflammation.
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“However, even minor increments in mechanical strain resulted and the activation of COX-2 and the production of PGE2, the basic biochemical mechanisms underlying tissue injury [54], and also in the production of interleukin-8 [65].”
From The pathophysiology of endometriosis and adenomyosis, tissue injury and repair (2009) · cites this paper as [54]
In the citing paper
“Following termination of unphysiological strain and healing, this process is down-regulated and the local production of estrogen or up-regulation of estrogen-dependent genes ceases [54, 57].”
From The pathophysiology of endometriosis and adenomyosis, tissue injury and repair (2009) · cites this paper as [54]
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Metadata
- Authors
- Yang, G., Im, H.-J., & Wang, J. H.-C.
- Affiliations
- University of Pittsburgh (US)
- Rush University Medical Center (US)
- Corresponding author
- Wang, James H.-C.
- Venue
- Gene
- Publisher
- Elsevier BV
- Published
- 2005-12
- Volume
- 363
- Pages
- 166-172
- ISSN
- 0378-1119 (ISSN-L)
- PMC
- PMC2901527
- OpenAlex
- W2082252073
- Cited by
- 282
- References
- 36
- Citations by year
- 2026: 11 · 2025: 9 · 2024: 5 · 2023: 12 · 2022: 15 · 2021: 10 · 2020: 19 · 2019: 17 · 2018: 13 · 2017: 15 · 2016: 14 · 2015: 20 · 2014: 13 · 2013: 13 · 2012: 22
- FWCI
- 8.09
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Gene (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Department of Veterans Affairs (I01BX002647)
- U.S. Public Health Service (049921)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR053220)
- Topics
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Tendon Structure and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Health Sciences › Medicine › Rheumatology › Osteoarthritis Treatment and Mechanisms
- Keywords
- IL-1β, cyclooxygenase-2, MMP-1, prostaglandin E2, tendon inflammation, tendon homeostasis, anti-inflammatory effects of exercise
- MeSH terms
- Adolescent, Adult, Base Sequence, Fibroblasts, Humans, Interleukin-1, Male, Patella, Physical Stimulation, Tendons, Dinoprostone, DNA Primers, Reverse Transcriptase Polymerase Chain Reaction, Matrix Metalloproteinase 1, Cyclooxygenase 2
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