Ferreira Natália Dos Reis, Sanz Carolina Kaminski, Raybolt Aline, Pereira Cláudia Maria, DosSantos Marcos Fabio
Faculty of Medicine, Institute of Occlusion and Orofacial Pain, University of Coimbra, Coimbra, Portugal.
Laboratório de Propriedades Mecânicas e Biologia Celular (PropBio), Departamento de Prótese e Materiais Dentários, Faculdade de Odontologia, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil.
Front Pain Res (Lausanne). 2022 Mar 18;3:852249. doi: 10.3389/fpain.2022.852249. eCollection 2022.
The temporomandibular joint is responsible for fundamental functions. However, mechanical overload or microtraumas can cause temporomandibular disorders (TMD). In addition to external factors, it is known that these conditions are involved in complex biological mechanisms, such as activation of the immune system, activation of the inflammatory process, and degradation of extracellular matrix (ECM) components. The ECM is a non-cellular three-dimensional macromolecular network; its most studied components is hyaluronic acid (HA). HA is naturally found in many tissues, and most of it has a high molecular weight. HA has attributed an essential role in the viscoelastic properties of the synovial fluid and other tissues. Additionally, it has been shown that HA molecules can contribute to other mechanisms in the processes of injury and healing. It has been speculated that the degradation product of high molecular weight HA in healthy tissues during injury, a low molecular weight HA, may act as damage-associated molecular patterns (DAMPs). DAMPs are multifunctional and structurally diverse molecules that play critical intracellular roles in the absence of injury or infection. However, after cellular damage or stress, these molecules promote the activation of the immune response. Fragments from the degradation of HA can also act as immune response activators. Low molecular weight HA would have the ability to act as a pro-inflammatory marker, promoting the activation and maturation of dendritic cells, the release of pro-inflammatory cytokines such as interleukin 1 beta (IL-1β), and tumor necrosis factor α (TNF-α). It also increases the expression of chemokines and cell proliferation. Many of the pro-inflammatory effects of low molecular weight HA are attributed to its interactions with the activation of toll-like receptors (TLRs 2 and 4). In contrast, the high molecular weight HA found in healthy tissues would act as an anti-inflammatory, inhibiting cell growth and differentiation, decreasing the production of inflammatory cytokines, and reducing phagocytosis by macrophages. These anti-inflammatory effects are mainly attributed to the interaction of high-weight HA with the CD44 receptor. In this study, we review the action of the HA as a DAMP and its functions on pain control, more specifically in orofacial origin (e.g., TMD).
颞下颌关节负责基本功能。然而，机械过载或微创伤可导致颞下颌关节紊乱病（TMD）。除外部因素外，已知这些病症涉及复杂的生物学机制，如免疫系统激活、炎症过程激活以及细胞外基质（ECM）成分降解。ECM是一种无细胞的三维大分子网络；其研究最多的成分是透明质酸（HA）。HA天然存在于许多组织中，且大部分具有高分子量。HA在滑液和其他组织的粘弹性特性中起着重要作用。此外，研究表明HA分子可在损伤和愈合过程中参与其他机制。据推测，在损伤期间健康组织中高分子量HA的降解产物，即低分子量HA，可能作为损伤相关分子模式（DAMPs）发挥作用。DAMPs是多功能且结构多样的分子，在无损伤或感染时在细胞内发挥关键作用。然而，在细胞损伤或应激后，这些分子会促进免疫反应的激活。HA降解产生的片段也可作为免疫反应激活剂。低分子量HA有能力作为促炎标志物，促进树突状细胞的激活和成熟、促炎细胞因子如白细胞介素1β（IL-1β）和肿瘤坏死因子α（TNF-α）的释放，还可增加趋化因子的表达和细胞增殖。低分子量HA的许多促炎作用归因于其与Toll样受体（TLRs 2和4）激活的相互作用。相比之下，健康组织中发现的高分子量HA将起到抗炎作用，抑制细胞生长和分化，减少炎性细胞因子的产生，并减少巨噬细胞的吞噬作用。这些抗炎作用主要归因于高分子量HA与CD44受体的相互作用。在本研究中，我们综述了HA作为DAMP的作用及其在疼痛控制方面的功能，更具体地是在口面部来源（如TMD）方面的功能。
