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

在我们以前的研究中，我们证明了透明质酸（HA）的分子量从颞下颌关节（TMJ）样本从内部紊乱和骨关节炎患者的滑液中减少。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，我们研究了几种分子量的HA对小鼠单核细胞系（RAW 264.7）中RANKL（NF-κ B配体的受体激活剂）诱导的破骨细胞形成和功能的影响。Mr<8，000的HA（低分子量HA（LMW-HA））以剂量依赖性方式增强RANKL诱导的抗酒石酸酸性磷酸酶-抗酸性磷酸酶活性，而Mr > 900，000的HA（高分子量HA（HMW-HA））对破骨细胞分化无影响。LMW-HA能促进RAW 264.7细胞诱导的陷窝形成，而HMW-HA则无此作用; LMW-HA能刺激RAW 264.7细胞中RANK（receptor activator of NF-kB）蛋白的表达。此外，我们发现LMW-HA增强了c-Src蛋白的水平和ERKS的磷酸化，而p38 MAPK抑制剂则抑制了RANKL诱导的破骨细胞分化。这些数据表明，LMW-HA在破骨细胞的分化和功能中起着重要作用，在颞下颌关节紊乱病中，HA的分子量降低。

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.