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Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_4 | Pages 80 - 80
1 Apr 2018
Ripmeester EGJ Caron MMJ van Rhijn LW Welting TJM
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Introduction

During osteoarthritis (OA) progression the articular chondrocyte undergoes a phenotypic switch in which the chondrocyte acquires a catabolic and hypertrophy-like state. Bone morphogenetic protein (BMP)-7 is known for its anti-catabolic and pro-anabolic properties in cartilage repair and in OA chondrocytes. In its anabolic state the chondrocyteā€¯s metabolism and protein synthesis are up-regulated. In order to meet a higher demand of protein synthesis, it is expected that the translational capacity of the chondrocyte is increased after exposure to BMP-7. The cellular availability of maturated ribosomal RNAs (rRNA) is rate-limiting in the assembly of ribosomes and previously it has been shown that BMP-7 treatment resulted in increased expression levels of bagpipe homeobox homolog 1 (BAPX-1/NKX3.2). We therefore hypothesize that BMP-7 enhances the translational capacity of articular chondrocytes via BAPX-1/NKX3.2-dependent synthesis of rRNAs.

Methods

OA human articular chondrocytes (HACs) were isolated from OA cartilage from total knee arthroplasty. SW1353 cells and OA HACs were exposed to BMP-7 (1 nM) and expression levels of rRNAs (18S, 5.8S, 28S) rRNA processing snoRNAs (RMRP and U3), a crucial co-factor in rRNA transcription (UBF-1) and BAPX-1/NKX3.2 were determined by RT-qPCR (and immunoblotting for BAPX-1/NKX3.2). BAPX-1/NKX3.2 overexpression and knockdown were achieved via transfection of FLAG-BAPX-1/NKX3.2 or a BAPX-1/NKX3.2 siRNA. For ex vivo confirmation, human OA cartilage explants from total knee arthroplasty were exposed to BMP-7 (1 nM) and gene expression levels of rRNAs were measured via qPCR.