Increased mandibular condylar growth in mice with estrogen receptor beta deficiency

Abstract

Temporomandibular joint (TMJ) disorders predominantly afflict women of childbearing age, suggesting a role for female hormones in the disease process. In long bones, estrogen acting via estrogen receptor beta (ERβ) inhibits axial skeletal growth in female mice. However, the role of ERβ in the mandibular condyle is largely unknown. We hypothesize that female ERβ deficient mice will have increased mandibular condylar growth compared with wild type (WT) female mice. This study examined female 7-, 49- and 120-day-old WT and ERβ knockout (KO) mice. There was a significant increase in mandibular condylar cartilage thickness, due to an increased number of cells, in the 49- and 120-day-old female ERβ KO compared with WT controls. Analysis in 49-day-old female ERβ KO mice revealed a significant increase in collagen type X, Pthrp and osteoprotegrin gene expression and a significant decrease in Rankl and Ihh gene expression, compared with WT controls. Subchondral bone analysis revealed a significant increase in total condylar volume and a decrease in the number of osteoclasts in the 49-day-old ERβ KO compared with WT female mice. There was no difference in cell proliferation in condylar cartilage between the genotypes. However, there were differences in the expression of proteins that regulate the cell cycle; we found a decrease in the expression of Tieg1 and p57 in the mandibular condylar cartilage from ERβ KO mice compared with WT mice. Taken together, our results suggest that ERβ deficiency increases condylar growth in female mice by inhibiting the fibrocartilage turnover.

Estrogen Aggravates Iodoacetate-induced Temporomandibular Joint Osteoarthritis

“…Our results are consistent with those from our previous report that estrogen aggravates CFA-induced TMJ inflammation via the estrogen receptor (Kou et al, 2011) and are also consistent with the results that estrogen inhibits chondrocyte proliferation through the estrogen receptor (Ikeda et al, 2012). Moreover, deficiency of estrogen receptor β increases mandibular condylar cartilage thickness in mice (Kamiya et al, 2013). Our results demonstrate that E2 aggravated the progression of MIA-induced TMJOA depending on the pathways of estrogen receptors.…”

Expression of estrogen receptors α and β in the trigeminal mesencephalic nucleus of adult women and men

“…Thus, it appears that respective brain regions receiving sensory inputs from the TMJ can sense estrogen. This is in addition to the already established belief that TMJ-tissue itself can sense estrogen (Aufdemorte et al, 1986;Abubaker et al, 1993;Kamiya et al 2013;Orajarvi et al, 2011;Wang et al, 2008). Estrogen-receptive sensory neurons are in line with the recent demonstration of ER in rodent dorsal root ganglia (Sohrabji et al, 1994;Papka et al, 1997).…”

“…Moreover, several lines of evidence indicate the impact of estrogen on cartilage and its metabolism (Breu et al, 2011;Claassen et al, 2001;Claassen et al, 2011;Kamiya et al, 2013;Schicht et al, 2014). In general, phases of pain usually develop after puberty and peak in the reproductive years (Meisler, 1999;Warren and Fried, 2001) with the highest prevalence appearing in women aged between 20 and 40 years and the lowest among children, adolescents and the elderly (Warren and Fried, 2001;Kuttila et al, 1998).…”

Sinais e sintomas de desordem temporomandibular em mulheres e homens

“…There is also evidence that the estrogen levels might act not only on metabolism, but also on the development and restitution of TMJ and associated structures, such as bones, cartilages, and joint disk, and they can influence the synthesis of collagen and elastin (which constitute the structure of the joint disk) (11) . Despite the potential of the estrogen to modulate multiple biological processes in the TMJ region, including inflammation, metalloproteinase activity, and pain modulation, none of these processes can fully explain the TMD predilection for the female gender, which suggests that other dependent mechanisms are also involved (21) . In addition, headache is a common complaint by many TMD patients, and it can be associated with pain in the muscles of mastication and TMJ, besides being more frequent in women (1,22) .…”