Increased chemokine RANTES in synovial fluid and its role in early-stage degenerative temporomandibular joint disease

J Oral Rehabil. 2020 Sep;47(9):1150-1160. doi: 10.1111/joor.13041. Epub 2020 Jul 13.


Background: Degenerative joint disease (DJD) of the temporomandibular joints (TMJs) in adolescents and young adults is closely associated with disc displacement without reduction (DDw/oR).

Objective: This study aimed to determine the pathogenesis of early-stage TMJ DJD induced by DDw/oR.

Methods: 31 female subjects aged 12-30 years were enrolled, comprising 12 patients with DDw/oR without DJD, 13 with DDw/oR and early-stage DJD, and 6 healthy volunteers. The synovial fluid samples of the subjects were screened for 27 inflammatory-related cytokines using multiple cytokine array. Significantly increased cytokines and a key regulator of osteoclastogenesis "receptor activator of nuclear factor-κB ligand" (RANKL) were further determined by sandwich immunoassay. These factors were also assessed for the possible pathophysiologic actions on RAW264.7 cell proliferation, migration, osteoclastogenesis and bone-resorbing activity using Cell Counting Kit-8, Transwell system, tartrate-resistant acid phosphatase staining and osteo assay plates.

Results: Macrophage-derived inflammatory protein-1 beta (MIP-1β) and regulated upon activation normal T cell expressed and secreted (RANTES) were found to vary significantly in relation to the controls. In contrast to an unchanged concentration of RANKL, a strong increase in the level of RANTES was detected in subjects with DDw/oR and early-stage DJD. MIP-1β concentrations were only elevated in subjects with DDw/oR without DJD. Functionally, both MIP-1β and RANTES could enhance macrophage migration in a concentration-dependent manner, while only RANTES exhibited a promoting effect on osteoclast formation and bone-resorbing activity.

Conclusions: Chemokine RANTES was significantly upregulated and might be a key regulator of osteoclastogenesis contributing to DDw/oR-induced early-stage TMJ DJD.

Keywords: adolescent; arthritis; bone; inflammatory processes/inflammatory markers; remodelling; temporomandibular disorders.

MeSH terms

  • Adolescent
  • Adult
  • Chemokine CCL5
  • Chemokines
  • Child
  • Female
  • Humans
  • Osteoclasts
  • RANK Ligand
  • Synovial Fluid*
  • T-Lymphocytes
  • Temporomandibular Joint
  • Temporomandibular Joint Disorders*
  • Young Adult


  • Chemokine CCL5
  • Chemokines
  • RANK Ligand