c-Jun transactivates Puma gene expression to promote osteoarthritis

Lu,Huading; Hou,Gang; Zhang,Yongkai; Dai,Yuhu; Zhao,Huiqing

doi:10.3892/mmr.2014.1981

c-Jun transactivates Puma gene expression to promote osteoarthritis

Authors:
- Huading Lu
- Gang Hou
- Yongkai Zhang
- Yuhu Dai
- Huiqing Zhao
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Affiliations: Department of Orthopaedics, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P.R. China
Published online on: February 24, 2014 https://doi.org/10.3892/mmr.2014.1981
Pages: 1606-1612

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Abstract

Osteoarthritis (OA) is a chronic degenerative joint disorder in which genetic, hormonal, mechanical and ageing factors affect its progression. Current studies are focusing on chondrocytes as a key mediator of OA at a cellular level. however, the mechanism underlying chondrocyte apoptosis remains unclear. PUMA is a pro-apoptotic member of the BH3-only subgroup of the Bcl-2 family and is involved in a large number of physiological and pathological processes. In the present study, we examined whether PUMA has a role in IL-1β‑induced apoptosis and whether the c-Jun N-terminal kinase (JNK)/c-Jun pathway mediates the induction of PUMA, thus contributing to chondrocyte apoptosis. The results demonstrated an increase in PUMA protein and mRNA levels in cultured mouse chondrocytes following 4 h of IL-1β treatment. Furthermore, this upregulation of PUMA was critical for chondrocyte apoptosis as knockdown of PUMA using PUMA-specific siRNA significantly reduced apoptosis in cultured cells. Upon pharmacological inhibition of the JNK/c-Jun pathway with CE11004 or SP600125, the expression of PUMA was notably suppressed with a concomitant decrease in apoptosis observed in IL-1β-treated chondrocytes. Also, immunohistochemical studies revealed that the PUMA and c-Jun proteins were upregulated in chondrocytes from the articular cartilage of OA patients. Together, these data suggest a role for PUMA and the JNK/c-Jun pathway in the regulation of chondrocyte apoptosis during OA.

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