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Laboratory and Clinical Studies on Hormonal Etiopathogenesis of Temporomandibular Joint (TMJ) Disorders
The purpose of these studies is to dissect the mechanisms by which female reproductive hormones, relaxin, estrogen, and progesterone, and their receptors contribute to the degeneration of temporomandibular joint (TMJ) fibrocartilage potentially contributing to temporomandibular disorders (TMDs). The symptoms of TMDs such as pain and limited jaw movement occur in approximately 10 million individuals in the USA. Because these disorders are highly prevalent in women of reproductive age, it has been hypothesized that female sex hormones contribute to the initiation or progression of these disorders. In support of this concept, we have previously demonstrated that relaxin and / or estrogen increase, and progesterone attenuates the expression of specific matrix metalloproteinase (MMP) tissue degrading enzymes and alter the matrix composition of the TMJ disc fibrocartilage. In our ongoing studies we are using specific gene knockout mice to dissect the contribution of particular hormone receptors and MMPs to the degradation of TMJ fibrocartilage in vivo. In order to determine whether studies in cells and animals have relevance to humans, we are also determining whether the systemic concentrations of sex hormones are different in women with TMJ diseases than in asymptomatic controls. Identification of the MMPs and receptors involved in hormone mediated degradation of TMJ fibrocartilage will provide early and specific therapeutic targets during reversible stages of the disease process that would be important in preventing or alleviating the progression of these disorders.
Mesenchymal Stems Cells and Mechanoplasticity
The focus of this research is to determine whether human mesenchymal stem cells (MSC), biologically induced to differentiate along a chondrocytic pathway, demonstrate optimal mechanoplasticity and mechanoresponsiveness within a specific window of time during the differentiation process. The goal of the proposed research is to develop a stem cell bioreactor system that enables the bioengineering of heterogenous tissues through biologic and mechanical modulation. These studies are being performed in collaboration with Dr. Jeffrey Lotz of the University of California San Francisco.
Fibronectin Fragment-induced Osteolysis Mediated by Matrix Metalloproteinases
Although MMPs have been implicated in periodontitis, their specific role in altering the equilibrium between bone synthesis and degradation during periodontal breakdown has not been investigated. The aim of these studies is to determine the contribution of specific MMPs induced by periodontal disease-associated fibronectin fragments in potentiating the disease by enhancing osteoclast activity and diminishing osteoblast differentiation of periodontal ligament cells.
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