The purpose of this core is to consolidate key personnel and equipment to provide a centralized facility to enhance collaborative and multidisciplinary investigations into the multiple mechanisms of osteoporosis in old age. Core C will perform six labor-intensive and highly specialized procedures in a cost- and timeefficient manner to facilitate the examination of the changes in bone cells, architecture, mass, and strength that accompany old age.
Aim 1. Prepare undecalcified, plastic-embedded, tetracycline-labeled bone sections to supply the project leaders with the materials necessary for a quantitative static and dynamic histological analysis of axial (lumbar vertebrae) and appendicular (distal femoral) bone. The core will also prepare sections by in-situ nick-end labeling to determine the prevalence of osteoblast and osteocyte apoptosis.
Aim 2. Obtain frozen sections of undecalcified bone using a dedicated cryostat and tape-transfer system to facilitate quantification of p-galactosidase activity, immunostaining of targeted cells in transgenic animals, and recognition of green fluorescent protein at the same time as tetracycline labels. These needs of the program cannot be accomplished with standard plastic-embedded or decalcified, paraffin-embedded sections. The core will also be responsible for freezer storage of these specimens.
Aim 3. Perform micro-CT measurements using a unique horizontal imaging system to acquire images comparable to those obtained by longitudinal sections for bone histology. In a customized specimen holder that accommodates a stack of 10 bones, lumbar vertebrae or femora will be scanned to determine the individual volumetric densitometric contributions of cortical and cancellous bone. In addition, three-dimensional measurements of cortical and cancellous microarchitecture will be done.
Aim 4. Provide murine bone mass determinations by dual-energy x-ray absorptiometry on Hologic or PIXImus instruments to meet the needs of the project leaders. Measurements of global, spinal, and femoral bone density will be performed serially, in longitudinal experiments, in live mice.
Aim 5. Acquire biomechanical measurements of murine vertebral compression strength and femoral three-point bending using a material testing system to determine the significance of changes in bone mineral density and bone architecture.
Aim 6. Train key personnel from the projects that need bone mass, biomechanical and histomorphometric measurements to help each team meet the goal of their projects. This centralized facility will provide for each of the projects a uniform and comprehensive investigation of the skeletal changes in bone mass, architecture, turnover and strength that occur with aging allowing determination of the efficacy of different treatment regimens in preventing fragility fractures.
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