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学科主题: 临床医学
题名:
Recovery of function in osteoarthritic chondrocytes induced by p16(INK4a)-specific siRNA in vitro
作者: Zhou, HW; Lou, SQ; Zhang, K
关键词: p16(INK4a) ; senescence ; osteoarthritis ; siRNA
刊名: RHEUMATOLOGY
发表日期: 2004-05-01
DOI: 10.1093/rheumatology/keh127
卷: 43, 期:5, 页:555-568
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Rheumatology
研究领域[WOS]: Rheumatology
关键词[WOS]: RAT ARTICULAR CHONDROCYTES ; INDUCED PREMATURE SENESCENCE ; ANTERIOR CRUCIATE LIGAMENT ; NORMAL HUMAN FIBROBLASTS ; EPIDERMAL GROWTH-FACTOR ; CELL-CYCLE ; LIFE-SPAN ; REPLICATIVE SENESCENCE ; TELOMERASE ACTIVITY ; RNA INTERFERENCE
英文摘要:

Objective. To demonstrate the roles of p(16INK4a) in the senescence of human chondrocytes and the progression of osteoarthritis (OA).

Methods. Immunohistochemistry and reverse transcriptase polymerase chain reaction (RT-PCR) were performed to examine p(16INK4a) expression in fetal, normal age-matched and OA cartilage, and Western blot was used in primary cultured chondrocytes from different origins. To explore a functional p(16INK4a) knockdown in OA chondrocytes, the primary cultured cells were treated with p16(INK4a)-specific small interfering ribonucleic acids (siRNAs). Expression of p16(INK4a), p14(ARF) and p53 was observed by Western blot and RT-PCR. The phosphorylation status of pRb, senescence-associated beta-galactosidase (SA-beta-gal), cell G(1)/S transition and cell proliferation were studied by Western blot, histological staining, H-3-thymidine incorporation and cell counts respectively. Expression of the collagen I, collagen II and aggrecan genes was measured by semiquantitative RT-PCR. To establish the response of chondrocytes to cytokines, cells were treated with transforming growth factor-beta1 (TGF-beta1) or interleukin-lalpha (IL-1alpha) and examined for incorporation of H-3-thymidine, H-3-proline and S-35-sulphate respectively.

Results. A significant increase of p16(INK4a) was detected in OA chondrocytes compared with normal age-matched and fetal chondrocytes (P < 0.01) in vivo and in vitro. Treated with p16(INK4a)-specific siRNAs, OA chondrocytes displayed a significant decrease in p16(INK4a) expression with an increase of phosphorylated pRb, but no alteration of p14(ARF) and p53 expression, followed by decreases of senescent features and increases in the expression of some chondrocyte-specific genes and overall repair capacity.

Conclusions. p16(INK4a) is instrumental in the senescence of human articular chondrocytes or OA. The reduction of p16(INK4a) by RNA interference (RNAi) contributed to the recovery of osteoarthritic chondrocytes, suggesting that p16(INK4a) may be a viable future therapeutic candidate.

语种: 英语
WOS记录号: WOS:000221297900003
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/62053
Appears in Collections:北京大学第三临床医学院_骨科_期刊论文

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作者单位: Peking Univ, Dept Orthopaed Surg, Hosp 3, Beijing 100083, Peoples R China

Recommended Citation:
Zhou, HW,Lou, SQ,Zhang, K. Recovery of function in osteoarthritic chondrocytes induced by p16(INK4a)-specific siRNA in vitro[J]. RHEUMATOLOGY,2004,43(5):555-568.
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