Publications by authors named "R N Rosier"

Purpose: Breast cancer treatments (chemotherapy and hormone therapy) can cause a rapid loss in bone mineral density, leading to osteoporosis and fractures later in life. Fortunately, preventative measures (vitamin D, exercise, etc.) can delay bone loss if employed early enough.

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Lead remains a significant environmental toxin, and we believe we may have identified a novel target of lead toxicity in articular chondrocytes. These cells are responsible for the maintenance of joint matrix, and do so under the regulation of TGF-β signaling. As lead is concentrated in articular cartilage, we hypothesize that it can disrupt normal chondrocyte phenotype through suppression of TGF-β signaling.

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Since transforming growing factor-β (TGF-β)/Smad signaling inhibits chondrocyte maturation, endogenous negative regulators of TGF-β signaling are likely also important regulators of the chondrocyte differentiation process. One such negative regulator, Ski, is an oncoprotein that is known to inhibit TGF-β/Smad3 signaling via its interaction with phospho-Smad3 and recruitment of histone deacetylases (HDACs) to the DNA binding complex. Based on this, we hypothesized that Ski inhibits TGF-β signaling and accelerates maturation in chondrocytes via recruitment of HDACs to transcriptional complexes containing Smads.

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Introduction: Increasing obesity and type 2 diabetes, in part due to the high-fat (HF) Western diet, parallels an increased incidence of osteoarthritis (OA). This study was undertaken to establish a causal relation between the HF diet and accelerated OA progression in a mouse model and to determine the relative roles of weight gain and metabolic dysregulation in this progression.

Methods: Five-week-old C57BL/6 mice were placed on HF (60% kcal) or low-fat (lean, 10% kcal) diets for 8 or 12 weeks before transecting the medial collateral ligament and excising a segment of the medial meniscus of the knee to initiate OA.

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Osteosarcoma is a devastating tumor of bone, primarily affecting adolescents. Osteosarcoma tumors are notoriously radioresistant. Radioresistant cancers, including osteosarcoma, typically exhibit a considerable potential for relapse and development of metastases following treatment.

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