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Lab Meeting

Lab Meeting . January 24, 2012. Osteoporosis. Clinical osteoporosis, defined as bone fracture related to decreased bone density, is on of the most physically debilitating conditions associated with aging.

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Lab Meeting

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  1. Lab Meeting January 24, 2012

  2. Osteoporosis • Clinical osteoporosis, defined as bone fracture related to decreased bone density, is on of the most physically debilitating conditions associated with aging. • In older people, the temporary immobilization associated with a facture often precipitates a period of reduced physical activity or permanent physical disability. • As the US population becomes increasingly older, understanding and minimizing aging-related bone lose is increasingly becoming a national priority.

  3. Indicates of Aging Human Bone • Decreased trabecular thickness • Decreased cortical bone • Increased bone porosity • Decreased bone formation rate • Decreased number of osteoblasts • Decreased number of osteoclasts • Increased number of adipocytes Jee WSS and Yao W J Musculoskel Neuron Interact 2001

  4. Current Models of Osteoporosis • Ovariectomy (Wronksi, et al. Calcif Tissue Int 1988; Wronksi, et al. Calcif Tissue Int 1989; Wronksi, et al. Calcif Tissue Int 1992; Kalu, DN Bone Miner 1991; Seedor, et al. J Bone Miner Res 1991; Black, et al. Calcif Tissue Int 1989) • Immobilization (Jee, et al. J Histotech 1997; Jee, WSS and Ma, YF Morphologie 1999) • Treatment with particular factors (ie glucocorticoid) (Weinstein, et al. J Clin Invest 1998; Mangolagas, et al. J Bone Miner Res 1999)

  5. Wrn-/-Terc-/- Aging Model • Dyskeratosis Congenita (DC) (Terc) • Werner syndrome (WS) (Wrn) • Accelerated aging diseases in humans (premature osteoporosis) • Terc-/- mice lack detectable telomerase activity and are viable for the six generations analyzed. Early generations of Terc-/- mice show little change in telomere length and no premature aging phenotypes. But in subsequent generations (5 to 6), the telomeres shrink and mice show a number of premature aging phenotypes, including gray hair, increased incidence of spontaneous malignancies, and decreased life-span. (Sci. Aging Knowl. Environ., 2003) • Wrn-/-Terc-/- mice have a low bone mass phenotype shown by DXA on 14.7 month old mice, and that age-related osteoporosis is the result of impaired osteoblast differentiation. (Pignolo, et al Aging Cell 2008)

  6. Trabecular Bone Parameters WT Wrn-/- Terc-/- Wrn-/-/Terc-/-

  7. Cortical Bone Parameters WT Wrn-/- Terc-/- Wrn-/-/Terc-/-

  8. WT Wrn-/-/Terc-/- 10x magnification

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