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Reviews in Endocrine and Metabolic Disorders

Erschienen in:

01.06.2006

Molecular backgrounds of age-related osteoporosis from mouse genetics approaches

verfasst von: Hiroshi Kawaguchi

Erschienen in: Reviews in Endocrine and Metabolic Disorders | Ausgabe 1-2/2006

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Abstract

Backgrounds underlying age-related bone loss can be classified into two categories: systemic abnormality and osteoblast dysfunction. The former includes insufficiency of vitamin D or estrogen, causing a negative balance of calcium metabolism. We propose the contribution of an aging-suppressing gene, klotho, as a novel systemic factor, as a mouse deficient in the klotho gene exhibits multiple aging phenotypes including osteopenia with a low bone turnover. As a factor intrinsic to osteoblasts, we investigated the role of PPARγ, a key regulator of adipocyte differentiation, based on the facts that osteoblasts and adipocytes share a common progenitor. Heterozygous PPARγ-deficient mice exhibited high bone mass by stimulating osteoblastogenesis from bone marrow progenitors, and this effect became prominent with aging, indicating involvement of PPARγ-dependent bone formation in the pathophysiology of age-related bone loss. The local environment of osteoblasts is mainly controlled by cytokines/growth factors, among which insulin-like growth factor-I (IGF-I) is the most possible candidate whose production and activity are decreased with aging. Bone phenotypes of deficient mice of insulin receptor substrates (IRS-1 and IRS-2), essential molecules for intracellular signaling of IGF-I, revealed that IRS-1 is essential to maintain bone turnover by up-regulating anabolic and catabolic functions of osteoblasts, while IRS-2 is needed to keep the predominance of the anabolic function over the catabolic function. A next task ahead of us will be to elucidate the network system of these factors underlying age-related osteoporosis.

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Titel: Molecular backgrounds of age-related osteoporosis from mouse genetics approaches
verfasst von: Hiroshi Kawaguchi
Publikationsdatum: 01.06.2006
Verlag: Kluwer Academic Publishers-Plenum Publishers
Erschienen in: Reviews in Endocrine and Metabolic Disorders / Ausgabe 1-2/2006
Print ISSN: 1389-9155
Elektronische ISSN: 1573-2606
DOI: https://doi.org/10.1007/s11154-006-9011-3

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