Mechanisms involved in enhancement of osteoclast formation and function by low molecular weight hyaluronic acid
Mechanisms involved in enhancement of osteoclast formation and function by low molecular weight hyaluronic acid
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DOI：
10.1074/jbc.m412740200
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发表时间：
2005-05-13
影响因子：
4.8
通讯作者：
Nishihara, T
中科院分区：
文献类型：
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作者：
Ariyoshi, W;Takahashi, T;Nishihara, T
透明质酸（HA）是细胞外基质的一种成分，已被证明在体内和体外的骨形成、骨吸收和骨矿化中起重要作用。我们在小鼠单核细胞系（RAW 264.7）中检测了不同分子量的HA对RANKL （nf - κ B配体受体激活剂）诱导的破骨细胞形成和功能的影响。HA atM(r) < 8000（低分子量HA (LMW-HA)）呈剂量依赖性增强RANKL诱导的耐酒石酸酸性磷酸酶阳性多核细胞形成和耐酒石酸酸性磷酸酶活性，而HA atM(r) < 90万（高分子量HA (HMW-HA)）对破骨细胞分化无影响。LMW-HA对RAW 264.7细胞的核坑形成有促进作用，而HMW-HA对核坑形成无促进作用，同时LMW-HA刺激RAW 264.7细胞中nf - κ B受体激活因子（receptor activator of nf - κ B）蛋白的表达。此外，我们发现lw - ha在RANKL刺激的RAW 264.7细胞中提高了c-Src蛋白水平以及ERKs和p38 MAPK的磷酸化水平，而p38 MAPK抑制剂SB203580则抑制了RANKL诱导的破骨细胞分化。LMW-HA诱导的c-Src和RANK蛋白的增强被CD44功能阻断单克隆抗体抑制。这些结果表明LMW-HA通过RANKL和RANK的相互作用在破骨细胞的分化和功能中发挥重要作用。
Hyaluronic acid ( HA) is a component of the extracellular matrix that has been shown to play an important role in bone formation, resorption, and mineralization both in vivo and in vitro. We examined the effects of HA at several molecular weights on osteoclast formation and function induced by RANKL ( receptor activator of NF-kappa B ligand) in a mouse monocyte cell line (RAW 264.7). HA atM(r) < 8,000 (low molecular weight HA (LMW-HA)) enhanced tartrate-resistant acid phosphatase-positive multinucleated cell formation and tartrate-resistant acid phosphatase activity induced by RANKL in a dose-dependent manner, whereas HA at M-r > 900,000 ( high molecular weight HA (HMW-HA)) showed no effect on osteoclast differentiation. LMW-HA enhanced pit formation induced by RAW 264.7 cells, whereas HMW-HA did not, and LMW-HA stimulated the expression of RANK (receptor activator of NF-kappa B) protein in RAW 264.7 cells. In addition, we found that LMW-HA enhanced the levels of c-Src protein and phosphorylation of ERKs and p38 MAPK in RAW 264.7 cells stimulated with RANKL, whereas the p38 MAPK inhibitor SB203580 inhibited RANKL-induced osteoclast differentiation. This enhancement of c-Src and RANK proteins induced by LMW-HA was inhibited by CD44 function-blocking monoclonal antibody. These results indicate that LMW-HA plays an important role in osteoclast differentiation and function through the interaction of RANKL and RANK.