Hyaluronic acid inhibits mRNA expression of proinflammatory cytokines and cyclooxygenase‐2/prostaglandin E₂ production via CD44 in interleukin‐1‐stimulated subacromial synovial fibroblasts from patients with rotator cuff disease

Abstract

A growing body of evidence supports use of intraarticular hyaluronic acid (HA) injection in patients with rotator cuff disease. However, the mechanism of its anti-inflammatory action has not been clarified. We examined the effects of HA on the expression of mRNAs for proinflammatory cytokines (IL-1b, IL-6, and TNF-a and COX-2/PGE 2 production in IL-1-stimulated subacromial-synovium fibroblasts (SSF) derived from patients with rotator cuff disease. Various concentrations of HA were added to monolayer SSF cultures in the presence of IL-1b. Gene expression levels were analyzed by quantitative real-time reverse transcription-polymerase chain reaction. Intracellular production of COX-2 was identified by Western blotting. PGE 2 concentrations in the culture media were measured by ELISA. CD44 blocking with OS/37 was performed to investigate the mechanism of action of HA. Immunofluorescence cytochemistry confirmed binding of HA and the presence of CD44 on SSF. Exogenous HA significantly and dose-dependently decreased expression of proinflammatory cytokine mRNAs and COX-2/PGE 2 production in IL-1-stimulated SSF. Pretreatment with OS/37 reversed the inhibitory effects of HA. These results provide a basis for explaining why HA is effective for the treatment of rotator cuff disease. ß

Hyaluronan modulates cell proliferation and mRNA expression of adhesion‐related procollagens and cytokines in glenohumeral synovial/capsular fibroblasts in adhesive capsulitis

“…21,24,25 Our immunohistochemical study identified binding of HA and expression of CD44 on GSCFs from patients with adhesive capsulitis (unpublished data), although CD44 blocking did not reverse the inhibitory effect of HA on adhesion-related collagen and cytokines We therefore consider that the adhesionpreventive effects of HA observed in the present study were exerted through a pathway other than CD44. Further studies are needed to clarify the precise mechanisms of the intracellular signal pathways involved.…”

“…In some experiments involving CD44 blocking, the cells were pretreated with OS/37 or subclass-matched nonspecific mouse IgG 1 before HA treatment. 21 …”

Effectiveness of the Anti-adhesive Agent Protescal after Arthroscopic Rotator Cuff Repair: A Retrospective Study

“…Some studies have suggested that HA acts as a physical barrier to tendon repair, whilst others have reported that its actions are only pharmacological. 6,16,17) According to a study by Mitsui et al., 18) HA has been shown to contribute to cell proliferation and to the expression of mRNA encoding pro-collagen alpha 1 (III), which is a precursor to type III collagen, but not of pro-collagen alpha 1 (I), which is a precursor to type I collagen; as a result of their findings, they proposed the adhesion barrier role of HA. Further, Oryan et al 15) reported that HA injection into injured flexor digitorum superficialis of rabbits reduced postoperative bleeding, odema, and inflammatory reactions.…”

Cationised gelatin and hyaluronic acid coating enhances polyethylene terephthalate artificial ligament graft osseointegration in porcine bone tunnels

“…As a component of the extracellular matrix, hyaluronic acid has been demonstrated to accelerate the healing of rabbit flexor tendons [9]. Particularly, hyaluronic acid has the high capacity to suppress and alleviate inflammation [10][11][12]. Cationised gelatin, as a positively charged polymer, has long been used as a highly valuable carrier system as it provides a universally effective way to enhance biocompatibility of the polymers [13][14][15].…”