MicroRNA-9 regulates survival of chondroblasts and cartilage integrity by targeting protogenin
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RESEARCH
Open Access
MicroRNA-9 regulates survival of chondroblasts and cartilage integrity by targeting protogenin Jinsoo Song1†, Dongkyun Kim1†, Churl-Hong Chun2 and Eun-Jung Jin1*
Abstract Background: Studies have shown the roles of miR-9 and its validated target, protogenin (PRTG) in the differentiation of chondroblasts to chondrocyte and in the pathogenesis of osteoarthritis (OA). We hypothesized that miR-9 plays a distinct role in endochondral ossification and OA pathogenesis and the present study was undertaken to identify this role. In the studies, chondroblasts were isolated from limb bud of chick and mouse embryos and articular chondrocytes were isolated from rabbit and human cartilage. Osteoarthritic chondrocytes were isolated from cartilage from patients undergoing total knee replacement. Using these cells, we analyzed the changes in the expression of genes and proteins, tested the expression level of miR-9, and applied a target validation system. We also performed functional study of miR-9 and PRTG. Results: With the progression of chondrogenesis, decreased miR-9 level was observed at the time of numerous apoptotic cell deaths. And chondrocytes isolated from normal human articular cartilage expressed miR-9, and this expression was significantly reduced in OA chondrocytes, especially decreased its expression in parallel with the degree of cartilage degradation. Over-expression of PRTG induced the activation of caspase-3 signaling and increased apoptosis. However, the co-treatment with the miR-9 precursor or PRTG-specific siRNA blocked this apoptotic signaling. Conclusion: This study shows that PRTG is regulated by miR-9, plays an inhibitory action on survival of chondroblasts and articular chondrocytes during chondrogenesis and OA pathogenesis. Keywords: PRTG, miR-9, Apoptotic cell death, Chondrogenesis, Osteoarthritis
Background Chondrogenesis is the earliest phase of skeletal development. Most long bones of vertebrates are formed through the process of endochondral ossification. This well-defined and coordinated process involves mesenchymal cell condensation and chondrogenic differentiation for proper cartilage and bone formation [1]. Several reports have shown that two MAPKs, ERK and p38MAPK, regulate chondrogenesis [2,3]. However, despite the importance of these MAPKs in the regulation of cartilage formation, relatively little is known about the involvement of another MAPK signaling pathway, c-jun N-terminal kinase (JNK). Several recent studies demonstrated the importance of JNK signaling during chondrogenesis [4-11]. Activin-A, a * Correspondence: [email protected] † Equal contributors 1 Department of Biological Sciences, College of Natural Sciences, Wonkwang University, Iksan, Chunbuk 570-749, South Korea Full list of author information is available at the end of the article
member of the transforming growth factor-β family, may suppress chondrocyte differentiation in ATDC5 cells via down-regulation of JNK [4] and reverse signaling of ephrin-B inhibited the attachment and migration of huma
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