Role of Microrna 455 Networks in Mesenchymal Cell Differentiation and Osteoarthritis

Fumiaki Ayabe¹, Shigeru Miyaki², Diana Brinson¹, Satoshi Yamashita³, Hiroyuki Nakahara¹, Koji Otabe¹, Stuart Duffy¹, Shawn Grogan⁴, Shuji Takada³, Martin K. Lotz¹ and Hiroshi Asahara⁵, ¹Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA, ²Department of Orthopaedic Surgery, Hiroshima University, Hiroshima, Japan, ³Department of Systems BioMedicine, National Research Institute for Child Health and Development, Tokyo, Japan, ⁴The Scripps Research Institute, La Jolla, CA, ⁵Molecular & Experimental Med, The Scripps Research Institute, La Jolla, CA

Meeting: 2012 ACR/ARHP Annual Meeting

Keywords: cartilage, inflammation and osteoarthritis

Session Information

Title: Biology and Pathology of Bone and Joint

Session Type: Abstract Submissions (ACR)

Background/Purpose: The objectives of this study were to identify cartilage specific microRNAs (miRNAs, miR-) that are regulated by SOX9 and are increased in chondrogenesis, to determine changes in osteoarthritic (OA) cartilage, and to investigate the role of miR-455-5p and miR-455-3p (miR-455s) in human chondrocytes.

Methods: To identify miRNAs specifically expressed in chondrocytes, we performed microarray and quantitative polymerase chain reaction (qPCR) on cultured mouse chondrocytes using adenovirally induced SOX9 transcription. The expression of miR-455s was analyzed by qPCR on human articular chondrocytes, human mesenchymal stem cells (MSCs). The expression of miR-455s was monitored during chondrogenic differentiation of human MSCs in pellet cultures as well as in human articular cartilage from both normal and OA knee joints. We tested the effects of interleukin-1b (IL-1b) on miR-455s expression. Double-stranded miR-455s (ds-miR-455s) was transfected into chondrocytes to identify changes in gene expression associated with OA.

Results: The expression of miR-455s mirrors SOX9 expression, with large differences between human chondrocytes and human MSCs. During chondrogenesis, miR-455s expression in MSC cultures increased in parallel with the expression of SOX9, MAF and COL10A1. Normal human articular cartilage expressed miR-455s, with significant reduction in OA tissue. In vitro treatment of chondrocytes with IL-1b suppressed miR-455s expression. Transfection of chondrocytes with ds-miR-455s down-regulated expression of inflammatory genes.

Conclusion: This study shows that miR-455s expression is altered in concert with other chondrocyte differentiation-related expression patterns. The reduction in miR-455s expression in OA cartilage and in response to IL-1b may contribute to the abnormal gene expression pattern characteristic of OA.

Disclosure:

F. Ayabe,
None;

S. Miyaki,
None;

D. Brinson,
None;

S. Yamashita,
None;

H. Nakahara,
None;

K. Otabe,
None;

S. Duffy,
None;

S. Grogan,
None;

S. Takada,
None;

M. K. Lotz,
None;

H. Asahara,
None.

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