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

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

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.

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.

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