Sexual dimorphism of estrogen-sensitized synoviocytes contributes to gender difference in temporomandibular joint osteoarthritis

Oral Dis. 2018 Nov;24(8):1503-1513. doi: 10.1111/odi.12905. Epub 2018 Aug 20.


Objectives: Temporomandibular joint osteoarthritis (TMJOA) is approximately twice as prevalent in women than in men. Synoviocytes are believed to play a critical role in joint inflammation. However, it is unknown whether synoviocytes from different genders possess sexual dimorphisms that contribute to female-predominant TMJOA.

Materials and methods: Freund's complete adjuvant combined with monosodium iodoacetate was used to induce TMJOA in female and male rats. Histologic and radiographic features were used to evaluate TMJOA. The expression of CD68, MCP-1, iNOS, and IL-1β was detected by immunohistochemistry and real-time PCR. Primary fibroblast-like synoviocytes (FLSs) isolated from the synovial membrane of female and male rats were used for in vitro experiments.

Results: Female rats showed aggravated TMJOA features as compared to male rats. Increased expression of iNOS and IL-1β was detected in synovial membrane from female TMJOA rats as compared to male rats. Furthermore, greater amounts of CD68-positive macrophage infiltration and increased MCP-1 expression around the synovial membrane were detected in female TMJOA rats compared to males. Primary cultured FLSs from female rats showed higher sensitivity to TNF-α treatment and recruited increased macrophage migration than male FLSs. More important, ovariectomy (OVX) by ablation in female rats repressed the sensitivity of female FLSs to TNF-α treatment due to the loss of estrogen production. Blockage of the estrogen receptor repressed estrogen-potentiated TNF-α-induced pro-inflammatory cytokine expression in OVX-FLSs. Moreover, the injection of estrogen receptor antagonists relieved the cartilage destruction and bone deterioration of TMJOA in female rats.

Conclusion: Estrogen-sensitized synoviocytes in female rats may contribute to gender differences in the incidence and progression of TMJOA.

Keywords: Temporomandibular joint osteoarthritis; estrogen; sexual dimorphism; synovitis.

MeSH terms

  • Animals
  • Antigens, CD / metabolism
  • Antigens, Differentiation, Myelomonocytic / metabolism
  • Cell Movement / drug effects
  • Cells, Cultured
  • Chemokine CCL2 / metabolism
  • Estrogen Receptor Antagonists / pharmacology
  • Estrogens* / metabolism
  • Estrogens* / pharmacology
  • Female
  • Interleukin-1beta / metabolism
  • Macrophages / metabolism
  • Macrophages / physiology
  • Male
  • Nitric Oxide Synthase Type II / metabolism
  • Osteoarthritis / metabolism*
  • Osteoarthritis / pathology
  • Ovariectomy
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Estrogen / antagonists & inhibitors
  • Sex Factors
  • Synovial Membrane / metabolism
  • Synoviocytes / drug effects
  • Synoviocytes / metabolism*
  • Temporomandibular Joint Disorders / metabolism*
  • Tumor Necrosis Factor-alpha / pharmacology


  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • CD68 protein, rat
  • Ccl2 protein, rat
  • Chemokine CCL2
  • Estrogen Receptor Antagonists
  • Estrogens
  • IL1B protein, rat
  • Interleukin-1beta
  • Receptors, Estrogen
  • Tumor Necrosis Factor-alpha
  • Nitric Oxide Synthase Type II
  • Nos2 protein, rat