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The mTORC1/4E-BP1 axis represents a critical signaling node during fibrogenesis.

January 2, 2019

Nat Commun

Abstract Myofibroblasts are the key effector cells responsible for excessive extracellular matrix deposition in multiple fibrotic conditions, including idiopathic pulmonary fibrosis (IPF). The PI3K/Akt/mTOR axis has been implicated in fibrosis, with pan-PI3K/mTOR inhibition currently under clinical evaluation in IPF. Here we demonstrate that rapamycin-insensitive mTORC1 signaling via 4E-BP1 is a critical pathway for TGF-β stimulated […]

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Identification of serological biomarker profiles associated with total joint replacement in osteoarthritis patients.

June 1, 2017

Osteoarthritis Cartilage

Abstract OBJECTIVE Establish a biomarker panel associated with all-cause total joint replacement (TJR) through identification of patients with osteoarthritis (OA) who do or do not progress to TJR and investigate effects of nonsteroidal anti-inflammatory drugs (NSAIDs). DESIGN Serum samples from patients enrolled in phase III trials of tanezumab who experienced TJR (n = 174) or matched patients […]

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Advances in osteoclast biology resulting from the study of osteopetrotic mutations.

January 1, 2009

Hum Genet

Abstract Osteopetrosis is the result of mutations affecting osteoclast function. Careful analyses of osteopetrosis have provided instrumental information on bone remodeling, including the coupling of bone formation to bone resorption. Based on a range of novel genetic mutations and the resulting osteoclast phenotypes, we discuss how osteopetrosis models have clarified the function of the coupling […]

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