Intra-Articular Injection of Hyaluronan Restores the Aberrant Expression of Matrix Metalloproteinase-13 in Osteoarthritic Subchondral Bone
Intra-Articular Injection of Hyaluronan Restores the Aberrant Expression of Matrix Metalloproteinase-13 in Osteoarthritic Subchondral Bone
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DOI：
10.1002/jor.21240
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发表时间：
2011-03-01
影响因子：
2.8
通讯作者：
Kubo, Toshikazu
中科院分区：
文献类型：
--
作者：
Hiraoka, Nobuyuki;Takahashi, Kenji A.;Kubo, Toshikazu
软骨下骨是治疗骨关节炎（OA）的候选骨。本研究观察了关节腔内注射透明质酸（JIM-HA）对兔OA模型软骨下骨的影响。通过前交叉韧带横断诱导OA，一些兔子接受IAI-HA。对OA进行形态学分级，并通过实时RT-PCR评估mRNA的表达。组织切片用透明质酸结合蛋白染色，并评估荧光透明质酸的渗透。采用实时荧光定量PCR和ELISA方法检测透明质酸对人骨关节炎软骨下骨成骨细胞（OA Oh）中MMP-13的抑制作用。通过免疫荧光细胞化学评估透明质酸通过CD 44与OA Ob的结合。软骨和软骨下骨中MMP-13和IL-6 mRNA的表达以及形态学OA分级随时间增加。IAI-HA可改善OA分级，并选择性抑制软骨下骨MMP-13 mRNA表达。IAI-HA增强软骨下骨髓细胞和骨细胞陷窝的透明质酸染色。在软骨下骨髓间隙中观察到荧光。在OA Ob中，透明质酸减少MMP-13的表达和产生，抗CD 44抗体阻断透明质酸与OA Ob的结合。这些结果表明，MMP-13在软骨下骨的调节可能是一个关键的机制，在IAI-HA。(C)2010骨科研究学会。出版社：Wiley Periodicals，Inc. J Orthop Res 29：354 360，2011
Subchondral bone is a candidate for treatment of osteoarthritis (OA). We investigated the effects of intra-articular injection of hyaluronan (JIM-HA) on subchondral bone in rabbit OA model. OA was induced by anterior cruciate ligament transection, with some rabbits receiving IAI-HA. OA was graded morphologically, and expression of mRNA was assessed by real-time RT-PCR. Tissue sections were stained with hyaluronan-binding protein, and penetration of fluorescent hyaluronan was assessed. The in vitro inhibitory effect of hyaluronan on MMP-13 was analyzed in human osteoarthritic subchondral bone osteoblasts (OA Oh) by real-time RT-PCR and ELISA. Binding of hyaluronan to OA Ob via CD44 was assessed by immunofluorescence cytochemistry. Expression of MMP-13 and IL-6 mRNA in cartilage and subchondral bone, and morphological OA grade, increased over time. IAI-HA ameliorated the OA grade and selectively suppressed MMP-13 mRNA in subchondral bone. IAI-HA enhanced the hyaluronan staining of subchondral bone marrow cells and osteocyte lacunae. Fluorescence was observed in the subchondral bone marrow space. In OA Ob, hyaluron an reduced the expression and production of MMP-13, and anti-CD44 antibody blocked hyaluronan binding to OA Ob. These findings indicate that regulation of MMP-13 in subchondral bone may be a critical mechanism during IAI-HA. (C) 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 29:354 360, 2011