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Decreased histone deacetylase 4 is associated with human osteoarthritis cartilage degeneration by releasing histone deacetylase 4 inhibition of runt-related transcription factor-2 and increasing osteoarthritis-related genes: a novel mechanism of human os
- 作者:Kun Cao (1)
Lei Wei (1) (2) Zhiqiang Zhang (1) Li Guo (1) Congming Zhang (1) Yongping Li (1) Changqi Sun (2) Xiaojuan Sun (2) Shaowei Wang (1) Pengcui Li (1) Xiaochun Wei (1)
- 刊名:Arthritis Research & Therapy
- 出版年:2014
- 出版时间:December 2014
- 年:2014
- 卷:16
- 期:6
- 全文大小:1,631 KB
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2. von der Mark K, Kirsch T, Nerlich A, Kuss A, Weseloh G, Glückert K, St?ss H: Type X collagen synthesis in human osteoarthritic cartilage. Indication of chondrocyte hypertrophy. / Arthritis Rheum 1992, 35:806-11. CrossRef 3. Aigner T, Reichenberger E, Bertling W, Kirsch T, Stoss H, Von der Mark K: Type X collagen expression in osteoarthritic and rheumatoid articular cartilage. / Virchows Archiv B Cell Pathol Incl Mol Pathol 1993, 63:205-11. CrossRef 4. Gouttenoire J, Valcourt U, Ronziere MC, Aubert-Foucher E, Mallein-Gerin F, Herbage D: Modulation of collagen synthesis in normal and osteoarthritic cartilage. / Biorheology 2004, 41:535-42. 5. Aigner T, Soder S, Gebhard PM, McAlinden A, Haag J: Mechanisms of disease: role of chondrocytes in the pathogenesis of osteoarthritis–structure, chaos and senescence. / Nat Clin Pract Rheumatol 2007, 3:391-99. CrossRef 6. Slagboom E, Meulenbelt I: Genetics of osteoarthritis: early developmental clues to an old disease. / Nat Clin Pract Rheumatol 2008, 4:563. CrossRef 7. Inada M, Wang Y, Byrne MH, Rahman MU, Miyaura C, López-Otín C, Krane SM: Critical roles for collagenase-3 (Mmp13) in development of growth plate cartilage and in endochondral ossification. / Proc Natl Acad Sci U S A 2004, 101:17192-7197. CrossRef 8. Wang Y, Middleton F, Horton JA, Reichel L, Farnum CE, Damron TA: Microarray analysis of proliferative and hypertrophic growth plate zones identifies differentiation markers and signal pathways. / Bone 2004, 35:1273-293. CrossRef 9. Kamekura S, Hoshi K, Shimoaka T, Chung U, Chikuda H, Yamada T, Uchida M, Ogata N, Seichi A, Nakamura K, Kawaguchi H: Osteoarthritis development in novel experimental mouse models induced by knee joint instability. / Osteoarthritis Cartilage 2005, 13:632-41. CrossRef 10. Kamekura S, Kawasaki Y, Hoshi K, Shimoaka T, Chikuda H, Maruyama Z, Komori T, Sato S, Takeda S, Karsenty G, Nakamura K, Chung UI, Kawaguchi H: Contribution of runt-related transcription factor 2 to the pathogenesis of osteoarthritis in mice after induction of knee joint instability. / Arthritis Rheum 2006, 54:2462-470. CrossRef 11. Pacifici M, Koyama E, Iwamoto M: Mechanisms of synovial joint and articular cartilage formation: recent advances, but many lingering mysteries. / Birth Defects Res C Embryo Today 2005, 75:237-48. CrossRef 12. Kirsch T, Swoboda B, Nah H: Activation of annexin II and V expression terminal differentiation, mineralization and apoptosis in human osteoarthritic cartilage. / Osteoarthritis Cartilage 2000, 8:294-02. Cr - 作者单位:Kun Cao (1)
Lei Wei (1) (2) Zhiqiang Zhang (1) Li Guo (1) Congming Zhang (1) Yongping Li (1) Changqi Sun (2) Xiaojuan Sun (2) Shaowei Wang (1) Pengcui Li (1) Xiaochun Wei (1)
1. Department of Orthopaedics, Second Hospital of Shanxi Medical University, Shanxi Key Laboratory of Bone and Soft Tissue Injury Repair, Taiyuan, China 2. Department of Orthopaedics and Department of Surgery, Warren Alpert Medical School of Brown University/Rhode Island Hospital (RIH), Providence, Rhode Island, USA
- ISSN:1478-6354
文摘
Introduction To investigate if decreased histone deacetylase 4 (HDAC4) is associated with human osteoarthritis (OA) cartilage degeneration by releasing HDAC4 inhibition of runt-related transcription factor-2 (Runx2) resulting in increase of OA cartilage degeneration-related genes. Methods The mRNA and protein levels of HDAC4, Runx2, matrix metalloproteinase (MMP)-13, Indian hedgehog (Ihh) and type X collagen were detected by performing real-time PCR (RT-PCR), western blotting and immunohistochemistry on specimens from human OA and normal cartilage. To further explore the mechanism of regulation of Runx2 and OA-related genes by HDAC4, changes in these OA-related genes were further quantified by RT-PCR after overexpression of HDAC4 and knockdown of HDAC4 by siRNA. Runx2 and MMP-13 promoter activities were measured by dual luciferase assays. Results The levels of HDAC4 in the cartilage from OA patients and healthy 40- to 60-year-old donors were decreased to 31% and 65% compared with specimens from 20- to 40-year-old healthy donors, respectively (P mRNA levels of Runx2, MMP1, MMP3, MMP-13, type X collagen, Ihh, ADAMTS-4 and -5, and increased the mRNA of type II collagen. In addition, the data also shows that overexpression of HDAC4 not only decreased the expression of interleukin (IL)-1β, Cox2 and iNos and increased the expression of aggrecan, but also partially blocked the effect of IL-1β on expression of catabolic events in human OA chondrocytes. HDAC4 also inhibited Runx2 promoter activity and MMP13 promotor activity in a dose-dependent manner. In contrast, inhibition of HDAC4 by TSA drug had an opposite effect. Conclusions Our study is the first to demonstrate that decreased HDAC4 contributes, at least in part, to the pathogenesis of OA cartilage degeneration. Thus, HDAC4 may have chondroprotective properties by inhibiting Runx2 and OA-related genes.
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