Mechanisms involved in degradation of temporomandibular joint resulting from the decrease in the molecular weight of hyaluronic acid.

在我们之前的研究中，我们证明了从内部紊乱和骨关节炎患者的颞下颌关节（TMJ）样本中提取的滑液中透明质酸（HA）的分子量降低。在本研究中，我们假设HA分子量的降低可能会影响TMJ的降解。然后，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-kB配体受体激活剂）诱导的破骨细胞形成和功能的影响。Mr<8,000（低分子量HA）的HA以剂量依赖性方式增强RANKL诱导的抗酒石酸酸性磷酸酶抗性酸性磷酸酶活性，而Mr为> 900,000（高分子量HA）的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对RAW 264.7细胞中NF-kB受体激活因子（receptor activator of NF-kB）蛋白表达有刺激作用。此外，我们发现lw - ha可提高c-Src蛋白水平和ERKs磷酸化水平，而p38 MAPK抑制剂可抑制rankl诱导的破骨细胞分化。这些数据表明LMW-HA在颞下颌疾病中破骨细胞分化和功能中起重要作用，HA分子量降低。

In our previous study, we demonstrated that the molecular weights of hyaluronic acid (HA) in synovial fluid from temporomandibular joint (TMJ) samples from patients with internal derangement and osteoarthritis are decrease. In this study, we hypothesized that the decreased in molecular weights of HA could affect on the degradation of TMJ. Then we examined the effects of HA at several molecular weights on osteoclast formation and function induced by RANKL (receptor activator of NF-kB ligand) in a mouse monocyte cell line (RAW 264.7). HA at Mr<8,000 (low molecular weight HA (LMW-HA)) enhanced tartrate-resistant acid phosphatase-resistant acid phosphatase activity induced by RANKL in a dose-dependent manner, whereas HA at Mr > 900,000 (high molecular weight (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-kB) protein in RAW 264.7 cells. In addition, we found that LMW-HA enhanced the levels of c-Src protein and phosphorylation of ERKs, whereas the p38 MAPK inhibitor inhibited RANKL-induced osteoclast differentiation. These data suggests LMW-HA plays a important role in osteoclast differentiation and function in temporomandibular disorders, in which molecular weight of HA is decreased.