滑膜發炎是骨關節炎發病的主要原因，發炎的滑膜通過合成軟骨溶解酵素和促發炎介質侵蝕軟骨並增強發炎過程。阻止關節炎滑膜纖維母細胞分泌軟骨分解?和炎性介質可減輕關節炎疾病。單核細胞在發炎症部位的浸潤及粘附在滑膜上是關節炎進展過程中的關鍵步驟。在關節炎發展過程中，數種不同的粘附因子調節單核細胞在關節微環境中的遷移和粘附，其中包括細胞粘附因子-1（ICAM-1）。 ICAM-1是單核細胞進入滑膜組織的關鍵調節劑，在關節炎患者的滑膜中會發現ICAM-1的高度表現，因此，滑膜液中ICAM-1表現的負調控被認為和關節炎活性的抑制與改善症狀有關。微核糖核酸（miRNA）控制靶基因在轉錄後水平的合成並抑制靶基因的表現。儘管尚未清楚微核糖核酸如何調節關節炎中ICAM-1的表現，但許多微核糖核酸都參與調節關節炎的發病機轉。促炎性脂肪細胞因子－內臟脂肪素（visfatin）是由骨髓、骨骼肌和肝臟中的內臟白色脂肪組織產生。通過刺激關節炎滑膜纖維母細胞中介白素-6 (interleukin-6; IL-6) 和腫瘤壞死因子-α (tumor necrosis factor-α; TNF-α) 的表現，內臟脂肪素有助於滑膜關節的破壞。目前尚未清楚內臟脂肪素在關節炎進展過程是如何影響ICAM-1及單核細胞的粘附。本研究，擬瞭解內臟脂肪素如何通過增加ICAM-1的表現來增加單核細胞對滑膜纖維母細胞的粘附。另外，微核糖核酸-320a表現的降低通過內臟脂肪素對單磷酸腺?活化蛋白質激?(adenosine 5'-monophosphate (AMP)-activated protein kinase; AMPK) 和p38信號路徑的影響，表示該脂肪因子可能是關節炎中合適的治療目標
Pathophysiological events that modulate the progression of structural changes in osteoarthritis (OA) include monocyte adhesion and infiltration, and synovial inflammation. In particular, the adhesion protein intercellular adhesion molecule type 1 (ICAM-1) promotes monocyte recruitment into the synovial tissue. Visfatin is an adipocyte hormone that promotes the release of inflammatory cytokines during OA progression. We report that visfatin enhances ICAM-1 expression in human OA synovial fibroblasts (OASFs) and facilitates the adhesion of monocytes with OASFs. Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) and p38 inhibitors, as well as their respective siRNAs, attenuated the effects of visfatin upon ICAM-1 synthesis and monocyte adhesion. We also describe how miR-320a negatively regulates visfatin-induced promotion of ICAM-1 expression and monocyte adhesion. We detail how visfatin affects ICAM-1 expression and monocyte adhesion with OASFs by inhibiting miR-320a synthesis via the AMPK and p38 signaling pathways.
