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UNLABELLED We applied MDCT for in vivo evaluation of the microarchitecture of human vertebrae. Microstructure parameters, such as structure model index, Euler's number, and bone volume fraction, revealed higher relative risk for prevalent vertebral fracture than did BMD obtained by DXA. Thus, microstructure analysis by MDCT, together with simultaneously(More)
Bone remodeling is performed by osteoclasts and osteoblasts at the bone surface. Inside of bone is a network of numerous osteocytes, whose specific function has remained an enigma. Here we describe a transgenic mouse model in which inducible and specific ablation of osteocytes is achieved in vivo through targeted expression of diphtheria toxin (DT)(More)
Osteoclasts are acid-secreting polykaryons that have high energy demands and contain abundant mitochondria. How mitochondrial biogenesis is integrated with osteoclast differentiation is unknown. We found that the transcription of Ppargc1b, which encodes peroxisome proliferator–activated receptor-γ coactivator 1β (PGC-1β), was induced during osteoclast(More)
Members of the Foxo family, Foxo1 (Fkhr), Foxo3 (Fkhrl1), and Foxo4 (Afx), are mammalian homologs of daf-16, which influences life span and energy metabolism in Caenorhabditis elegans. Mammalian FOXO proteins also play important roles in cell cycle arrest, apoptosis, stress resistance, and energy metabolism. In this study, we generated Foxo1-deficient mice(More)
Forkhead transcription factor, DAF-16, regulates genes that contribute both to longevity and resistance to various stresses in C. elegans. We and others have reported that members of the FOXO, mammalian homologs of DAF-16, also regulate genes related to stress resistance, such as GADD45. The NAD-dependent protein deacetylase, SIR2, is required for life span(More)
The mammalian Chk2 kinase is thought to mediate ATM-dependent signaling in response to DNA damage. The physiological role of mammalian Chk2 has now been investigated by the generation of Chk2-deficient mice. Although Chk2(-/-) mice appeared normal, they were resistant to ionizing radiation (IR) as a result of the preservation of splenic lymphocytes.(More)
The ubiquitin-proteasome system (UPS) is critical for specific degradation of cellular proteins and plays a pivotal role on protein breakdown in muscle atrophy. Here, we show that ZNF216 directly binds polyubiquitin chains through its N-terminal A20-type zinc-finger domain and associates with the 26S proteasome. ZNF216 was colocalized with the aggresome,(More)
Members of the FOXO family of mammalian forkhead transcription factors, including AFX, FKHRL1, and FKHR, are homologs of DAF-16, which regulates genes that contribute both to longevity and to resistance to various stresses (including oxidative stress) in Caenorhabditis elegans. We have generated mouse myoblastic C2C12 cell lines in which expression of a(More)
Hypertension and osteoporosis are two major age-related disorders; however, the underlying molecular mechanism for this comorbidity is not known. The renin-angiotensin system (RAS) plays a central role in the control of blood pressure and has been an important target of antihypertensive drugs. Using a chimeric RAS model of transgenic THM (Tsukuba(More)
In order to determine whether the renin-angiotensin system (RAS) has any physiologic function in bone metabolism, mice lacking the gene encoding the major angiotensin II receptor isoform, AT1a, were studied using micro CT scanning, histomorphometric, and biochemical techniques. Three-dimensional (3D) micro CT analysis of the tibial metaphysis revealed that(More)