alexa Mouse Genetics Studies on Molecular Mechanisms Underlying Skeletal Disorders
ISSN: 2329-9509

Journal of Osteoporosis and Physical Activity
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Review Article

Mouse Genetics Studies on Molecular Mechanisms Underlying Skeletal Disorders

Hiroshi Kawaguchi*

Spine Center, Japan Community Health Care Organization (JCHO), Tsukudo 5-1, Tokyo 162-8543, Japan

*Corresponding Author:
Hiroshi Kawaguchi, M.D., Ph.D.
The Chief of the Spine Center, Japan Community Health Care Organization (JCHO)
Tsukudo 5-1, Tokyo 162-8543, Japan
Tel: 03-3269-8111
Fax: 03-3260-7840
E-mail: [email protected]

Received date: Dec 01, 2016; Accepted date: Mar 10, 2016; Published date: Mar 17, 2016

Citation: Kawaguchi H (2016) Mouse Genetics Studies on Molecular Mechanisms Underlying Skeletal Disorders. J Osteopor Phys Act 4:175. doi:10.4172/2329-9509.1000175

Copyright: © 2016 Kawaguchi H. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.



This paper summarizes our mouse genetics studies on the molecular backgrounds of representative degenerative skeletal diosrders: osteoporosis, ossification of the posterior longitudinal ligament of the spine (OPLL), and bone fracture healing. By analyzing deficient mice, PPARγ, a key adipogenesis molecule intrinsic to bone marrow progenitors, was shown to be involved in age-related osteoporosis. Studies on deficient mice and OPLL patients revealed that insulin and insulin-like growth factor-I (IGF-I) are potent bone anabolic factors through the balance of distinct signals of the two adaptor molecules, insulin receptor substrate (IRS)-1 and IRS-2: IRS-1 for maintenance of bone turnover by up-regulating anabolic and catabolic functions of osteoblasts, while IRS-2 for retaining the predominance of the anabolic function over the catabolic function. IRS-1 was also essential for bone fracture healing. These molecules could be therapeutic targets for the skeletal disorders.


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