Contribution of runt‐related transcription factor 2 to the pathogenesis of osteoarthritis in mice after induction of knee joint instability
Abstract
Objective: By producing instability in mouse knee joints, we attempted to determine the involvement of runt‐related transcription factor 2 (RUNX‐2), which is required for chondrocyte hypertrophy, in the development of osteoarthritis (OA). Methods: An experimental mouse OA model was created by surgical transection of the medial collateral ligament and resection of the medial meniscus of the knee joints of heterozygous RUNX‐2–deficient (Runx2+/−) mice and wild‐type littermates. Cartilage destruction and osteophyte formation in the medial tibial cartilage were compared by histologic and radiographic analyses. Localization of type X collagen and matrix metalloproteinase 13 (MMP‐13) was examined by immunohistochemistry. Localization of RUNX‐2 was determined by X‐Gal staining in heterozygous RUNX‐2–deficient mice with the lacZ gene insertion at the Runx2‐deletion site (Runx2+/lacZ). Messenger RNA levels of type X collagen, MMP‐13, and RUNX‐2 were examined by real‐time reverse transcriptase–polymerase chain reaction analysis. Results: RUNX‐2 was induced in the articular cartilage of wild‐type mice at the early stage of OA, almost simultaneously with type X collagen but earlier than MMP‐13. Runx2+/− and Runx2+/lacZ mice showed normal skeletal development and articular cartilage; however, after induction of knee joint instability, they exhibited decreased cartilage destruction and osteophyte formation, along with reduced type X collagen and MMP‐13 expression, as compared with wild‐type mice. Conclusion: RUNX‐2 contributes to the pathogenesis of OA through chondrocyte hypertrophy and matrix breakdown after the induction of joint instability.
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An imbalance between anabolic and catabolic factors within chondrocytes may cause osteoarthritic cartilage destruction.
“An imbalance between anabolic and catabolic factors within chondrocytes may cause osteoarthritic cartilage destruction [3-5].”
From Arthropod steroid hormone (20-Hydroxyecdysone) suppresses IL-1β- induced catabolic gene expression in cartilage (2015) · cites this paper as [5]
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- Authors
- Kamekura, S., Kawasaki, Y., Hoshi, K., Shimoaka, T., Chikuda, H., Maruyama, Z., Komori, T., Sato, S., Takeda, S., Karsenty, G., Nakamura, K., Chung, U., & Kawaguchi, H.
- Affiliations
- The University of Tokyo (JP)
- Nagasaki University (JP)
- Tokyo Medical and Dental University (JP)
- ORCID
- Venue
- Arthritis & Rheumatism
- Publisher
- Wiley
- Published
- 2006-07-25
- Volume
- 54
- Issue
- 8
- Pages
- 2462-2470
- ISSN
- 0004-3591 (ISSN-L)
- 1529-0131
- OpenAlex
- W1983579606
- Cited by
- 319
- References
- 49
- Citations by year
- 2026: 4 · 2025: 8 · 2024: 15 · 2023: 10 · 2022: 11 · 2021: 11 · 2020: 12 · 2019: 21 · 2018: 17 · 2017: 19 · 2016: 19 · 2015: 12 · 2014: 19 · 2013: 25 · 2012: 20
- FWCI
- 10.94
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Arthritis & Rheumatism (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Rheumatology › Osteoarthritis Treatment and Mechanisms
- Health Sciences › Medicine › Surgery › Hip disorders and treatments
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone and Joint Diseases
- Keywords
- Runx2, osteoarthritis, knee instability, medial collateral ligament transection, medial meniscectomy, chondrocyte hypertrophy, articular cartilage degeneration, osteophyte formation, type X collagen, matrix metalloproteinase-13, cartilage matrix degradation
- MeSH terms
- Tibial Meniscus Injuries, Animals, Cartilage, Articular, Disease Models, Animal, Joint Instability, Menisci, Tibial, Mice, Inbred C57BL, Osteoarthritis, RNA, Messenger, Stifle, Gene Deletion, Collagenases, Medial Collateral Ligament, Knee, Mice, Knockout, Collagen Type X, Core Binding Factor Alpha 1 Subunit, Mice, Matrix Metalloproteinase 13
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