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Estrogen Promotes Mandibular Condylar Fibrocartilage Chondrogenesis and Inhibits Degeneration via Estrogen Receptor Alpha in Female Mice
Robinson, Jennifer L. Soria, Paola Xu, Manshan Vrana, Mark Luchetti, Jeffrey Lu, Helen H. Chen, Jing Wadhwa, Sunil
Robinson, Jennifer L.
Soria, Paola
Xu, Manshan
Vrana, Mark
Luchetti, Jeffrey
Lu, Helen H.
Chen, Jing
Wadhwa, Sunil
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Abstract
Temporomandibular joint degenerative disease (TMJ-DD) is a chronic form of TMJ disorder that
specifically afflicts people over the age of 40 and targets women at a higher rate than men. Prevalence
of TMJ-DD in this population suggests that estrogen loss plays a role in the disease pathogenesis.
Thus, the goal of the present study was to determine the role of estrogen on chondrogenesis and
homeostasis via estrogen receptor alpha (ERα) during growth and maturity of the joint. Young and
mature WT and ERαKO female mice were subjected to ovariectomy procedures and then given placebo
or estradiol treatment. The effect of estrogen via ERα on fibrocartilage morphology, matrix production,
and protease activity was assessed. In the young mice, estrogen via ERα promoted mandibular
condylar fibrocartilage chondrogenesis partly by inhibiting the canonical Wnt signaling pathway
through upregulation of sclerostin (Sost). In the mature mice, protease activity was partly inhibited
with estrogen treatment via the upregulation and activity of protease inhibitor 15 (Pi15) and alpha-2-
macroglobulin (A2m). The results from this work provide a mechanistic understanding of estradiol on
TMJ growth and homeostasis and can be utilized for development of therapeutic targets to promote
regeneration and inhibit degeneration of the mandibular condylar fibrocartilage.
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2018-06-04
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Nature Research
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Robinson, Jennifer L et al. “Estrogen Promotes Mandibular Condylar Fibrocartilage Chondrogenesis and Inhibits Degeneration via Estrogen Receptor Alpha in Female Mice.” Scientific reports vol. 8,1 8527. 4 Jun. 2018, doi:10.1038/s41598-018-26937-w