Calcitonin affects both bone and cartilage: a dual action treatment for osteoarthritis?

November 1, 2007

Ann N Y Acad Sci

Abstract Osteoarthritis (OA) is the most common form of degenerative joint diseases and a major cause of disability and impaired quality of life in the elderly. OA is a complex disease involving both bone and cartilage properties, and may therefore require alternative approaches for treatment. Recent lines of evidence suggest that calcitonin acts on both […]

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Diphyllin, a novel and naturally potent V-ATPase inhibitor, abrogates acidification of the osteoclastic resorption lacunae and bone resorption.

October 1, 2007

J Bone Miner Res

Abstract UNLABELLED Dissolution of the inorganic phase of bone by the osteoclasts mediated by V-ATPase and ClC-7 is a prerequisite for bone resorption. Inhibitors of osteoclastic V-ATPase or ClC-7 are novel approaches for inhibition of osteoclastic bone resorption. By testing natural compounds in acidification assays, diphyllin was identified. We characterized diphyllin with respect to the […]

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Dissolution of the inorganic phase of bone leading to release of calcium regulates osteoclast survival.

September 7, 2007

Biochem Biophys Res Commun

Abstract Osteoclasts are the sole cells possessing the ability to resorb calcified bone matrix. This occurs via secretion of hydrochloric acid mediated by the V-ATPase and the chloride channel ClC-7. Loss of acidification leads to osteopetrosis characterized by ablation of bone resorption and increased osteoclast numbers, indicating increased life span of the osteoclasts. To investigate […]

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The effect of oral calcitonin on cartilage turnover and surface erosion in an ovariectomized rat model.

August 1, 2007

Arthritis Rheum

Abstract OBJECTIVE To investigate whether oral calcitonin treatment influences the increases in type II collagen (CII) degradation and related surface erosions of articular cartilage in ovariectomized rats. METHODS Fifty rats were randomly allocated into 1 of the 5 following intervention groups: sham-operated, ovariectomy, ovariectomy plus subcutaneously implanted 17beta-estradiol pellet, ovariectomy plus 2 mg/kg salmon calcitonin […]

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Assessment of osteoclast number and function: application in the development of new and improved treatment modalities for bone diseases.

May 1, 2007

Osteoporos Int

Abstract Numerous experimental and clinical observations suggest that overall changes in bone resorption during menopause or treatment with hormone replacement therapy (HRT) are combined effects of changes in osteoclast number and function. Moreover, due to a coupling between osteoclastic bone resorption and osteoblastic bone formation, pronounced alteration of osteoclast number will eventually lead to alteration […]

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Induction of increased cAMP levels in articular chondrocytes blocks matrix metalloproteinase-mediated cartilage degradation, but not aggrecanase-mediated cartilage degradation.

May 1, 2007

Arthritis Rheum

Abstract OBJECTIVE Calcitonin has been suggested to have chondroprotective effects. One signaling pathway of calcitonin is via the second messenger cAMP. We undertook this study to investigate whether increased cAMP levels in chondrocytes would be chondroprotective. METHODS Cartilage degradation was induced in bovine articular cartilage explants by 10 ng/ml oncostatin M (OSM) and 20 ng/ml […]

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Are nonresorbing osteoclasts sources of bone anabolic activity?

April 1, 2007

J Bone Miner Res

Abstract Some osteopetrotic mutations lead to low resorption, increased numbers of osteoclasts, and increased bone formation, whereas other osteopetrotic mutations lead to low resorption, low numbers of osteoclasts, and decreased bone formation. Elaborating on these findings, we discuss the possibility that osteoclasts are the source of anabolic signals for osteoblasts. In normal healthy individuals, bone […]

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Anabolic and catabolic function of chondrocyte ex vivo is reflected by the metabolic processing of type II collagen.

March 1, 2007

Osteoarthritis Cartilage

Abstract OBJECTIVE The aim of the present study was to investigate collagen metabolism after anabolic and catabolic stimulation of chondrocytes ex vivo. DESIGN Metabolic activities in ex vivo bovine cartilage explants were stimulated with insulin-like growth factor I (IGF-I) or a combination of tumor necrosis factor alpha (TNFalpha) and oncostatin M (OSM). Supernatants were assessed […]

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MMP and non-MMP-mediated release of aggrecan and its fragments from articular cartilage: a comparative study of three different aggrecan and glycosaminoglycan assays.

February 1, 2007

Osteoarthritis Cartilage

Abstract OBJECTIVE Aggrecan is the major proteoglycan in articular cartilage and is known to be degraded by various proteases, including matrix metalloproteinases (MMPs). The present study was undertaken to develop immunoassays detecting aggrecan and its fragments generated by MMP and non-MMP-mediated proteolysis. METHODS Two immunoassays were developed: (1) the G1/G2 sandwich assay employing a monoclonal […]

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