The long-term goal of our research is to understand the mechanisms regulating growth and differentiation of mandibular condylar cartilage. The mandibular condylar cartilage is derived from periosteum and comprised of 4 zones that contain cells at various stages of endochondral ossification. The mandibular condylar cartilage remodels in response to external mechanical strains by regulating chondrogenesis and endochondral ossification, in order to achieve a better balance between mechanical stress and the load bearing capacity of the joint. Estrogen regulates mandibular condylar cartilage growth and differentiation. It is known that the estrogen-mediated inhibition of mechanical loading-induced periosteal bone formation and axial skeletal growth requires estrogen receptor beta (ER?). However, the mechanisms underlying the regulatory effects of estrogen in the mandibular condylar cartilage remain unknown. The general objective of this application is to examine the effects of estrogen status on the regulation of mandibular condylar cartilage growth induced by mechanical loading. Our central hypothesis is that estrogen acts through ER? to inhibit chondrocyte maturation in the mandibular condylar cartilage in female mice and will, therefore, affect the response of condylar cartilage to mechanical stress. To test this hypothesis, the following Specific Aims will be examined;
Specific Aim 1 : Examine mandibular condylar growth in ER? deficient mice. Basal Mandibular condylar cartilage growth and differentiation in male and female wild type (WT) and ER2 deficient mice will be assessed. In addition, mandibular condylar growth will be examined in sham or ovariectomized WT and ER? deficient mice treated with or without estrogen.
Specific Aim 2 : Examine the role of ER? in the regulation of mandibular condylar cartilage differentiation in TMJ loading models. Two in vivo TMJ mechanical loading models, which cause either an increase or a decrease in mandibular chondrocyte differentiation, will be applied to male and female WT and ER? deficient mice. Mandibular condylar growth and differentiation will be assessed from both models. Greater understanding on how mandibular condylar cartilage remodeling is controlled by estrogen and mechanical loading will aid in the understanding of diseases of the temporomandiblar joint (TMD), which have a predilection for women between the ages of 18 and 45, and may also lead to new approaches to joint regeneration.

Public Health Relevance

Approximately, 10% of the United Sates population has suffered from temporomandibular joint disorders (TMD). TMD predominantly affects women of childbearing ages, but the reasons behind this are unknown. This proposal examines the mechanism behind estrogen inhibition of growth and differentiation of the mandibular condylar cartilage, which will give further insight into the age and gender predilection of TMD.

National Institute of Health (NIH)
National Institute of Dental & Craniofacial Research (NIDCR)
Research Project (R01)
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Skeletal Biology Development and Disease Study Section (SBDD)
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Lumelsky, Nadya L
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University of Connecticut
Schools of Dentistry
United States
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Robinson, J L; Cass, K; Aronson, R et al. (2017) Sex differences in the estrogen-dependent regulation of temporomandibular joint remodeling in altered loading. Osteoarthritis Cartilage 25:533-543
Polur, Ilona; Kamiya, Yosuke; Xu, Manshan et al. (2015) Oestrogen receptor beta mediates decreased occlusal loading induced inhibition of chondrocyte maturation in female mice. Arch Oral Biol 60:818-24
Chen, J; Kamiya, Y; Polur, I et al. (2014) Estrogen via estrogen receptor beta partially inhibits mandibular condylar cartilage growth. Osteoarthritis Cartilage 22:1861-8
Kamiya, Yosuke; Chen, Jing; Xu, Manshan et al. (2013) Increased mandibular condylar growth in mice with estrogen receptor beta deficiency. J Bone Miner Res 28:1127-34
Chen, J; Utreja, A; Kalajzic, Z et al. (2012) Isolation and characterization of murine mandibular condylar cartilage cell populations. Cells Tissues Organs 195:232-43
Chen, J; Sobue, T; Utreja, A et al. (2011) Sex differences in chondrocyte maturation in the mandibular condyle from a decreased occlusal loading model. Calcif Tissue Int 89:123-9
Sobue, T; Yeh, W-C; Chhibber, A et al. (2011) Murine TMJ loading causes increased proliferation and chondrocyte maturation. J Dent Res 90:512-6