Hyaluronic acid (HA) is one of the major components of the extracellular matrix (ECM), and hyaluronic acid synthase 2 (HAS2) is a key enzyme regulating its production. It has been reported that HA and HAS2 play crucial roles in inflammation by regulating cell function and cell communication. Our study aims to explore the roles of HA and HAS2 in periodontitis in vivo and in vitro, and investigates whether HA may influence the progression of periodontitis through cell communication. Gingival tissues were collected for reverse transcription quantitative polymerase chain reaction (RT-qPCR), immunohistochemistry, and immunofluorescence. siRNA was used to knock down the expression of HAS2 in human periodontal ligament cells (HPDLCs) and human gingival fibroblasts (HGFs). A ligature-induced periodontitis model was created and treated with an HA-specific inhibitor, 4-methylumbelliferone (4-MU). Finally, THP-1 cells were co-cultured with HGFs, and Western Blot was used to study the role of HGFs in influencing macrophages through the secretion of HA in periodontal inflammation. HA and HAS2 were highly expressed in inflammatory gingiva. Knockdown of HAS2 or inhibition of HA synthesis suppressed the levels of inflammatory cytokines in HGFs and HPDLCs. Pre-treatment of HGFs with 4-MU and co-culturing with THP-1 cells significantly reduced the levels of inflammatory cytokines in THP-1 cells. Administration of 4-MU alleviated alveolar bone loss in mice with periodontitis. Decreasing HA and HAS2 expression can alleviate periodontal inflammation, which may be achieved by influencing the interaction between fibroblasts and macrophages. 4-MU, an oral drug with a targeted inhibitory effect on HA synthesis, may have a therapeutic effect on periodontitis. • We demonstrated that LMW-HA predominates and exerts primarily pro-inflammatory effects in this context. • In the periodontal inflammatory milieu, where HA is primarily secreted by stromal cells (HGFs and HPDLCs), we discovered that stromal cell-derived HA may influence macrophage behavior. • 4-MU, an oral drug with a targeted inhibitory effect on HA synthesis, may have a therapeutic effect on periodontitis.
Wang et al. (Thu,) studied this question.