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Bone cells are organized into an interconnected network, which extends from the osteocytes within bone to the osteoblasts and lining cells on the bone surfaces. There is experimental evidence suggesting that bone tissue exhibits basic properties of short- and long-term memory. An analogy might be made between the bone cell network and neuronal systems. For(More)
Laboratory mice provide a versatile experimental model for studies of skeletal biomechanics. In order to determine the strength of the mouse skeleton, mechanical testing has been performed on a variety of bones using several procedures. Because of differences in testing methods, the data from previous studies are not comparable. The purpose of this study(More)
The effectiveness of exercise on bone strength depends on its type, timing, and duration R egular exercise has effects on bone density, size, and shape, resulting in substantial improvements in mechanical strength. The positive association between exercise and bone mass has prompted many physicians and public health officials to recommend that people engage(More)
The human skeleton is affected by mutations in low-density lipoprotein receptor-related protein 5 (LRP5). To understand how LRP5 influences bone properties, we generated mice with osteocyte-specific expression of inducible Lrp5 mutations that cause high and low bone mass phenotypes in humans. We found that bone properties in these mice were comparable to(More)
Osteocytes, former osteoblasts buried within bone, are thought to orchestrate skeletal adaptation to mechanical stimuli. However, it remains unknown whether hormones control skeletal homeostasis through actions on osteocytes. Parathyroid hormone (PTH) stimulates bone remodeling and may cause bone loss or bone gain depending on the balance between bone(More)
Neurofibromatosis type I (NF1) is a congenital disorder resulting from loss-of-function of the tumor suppressor gene, NF1, a GTPase-activating protein for p21ras. Fifty percent of NF1 patients have osseous manifestations including a high incidence of osteoporosis. Osteoclasts are specialized macrophage/monocyte lineage-derived cells that resorb bone and NF1(More)
Mechanical loading is essential to maintain normal bone metabolism and the balance between bone formation and resorption. The cellular mechanisms that control mechanotransduction are not fully defined, but several key pathways have been identified. We discuss the roles of several components of the Wnt signaling cascade, namely Lrp5, Lrp6, and β-catenin in(More)
Germline mutations in the NF1 tumor suppressor gene cause neurofibromatosis type 1 (NF1), a complex genetic disorder with a high predisposition of numerous skeletal dysplasias including short stature, osteoporosis, kyphoscoliosis, and fracture non-union (pseudoarthrosis). We have developed murine models that phenocopy many of the skeletal dysplasias(More)
A number of in vivo skeletal loading models have been developed to test specific hypotheses addressing the key mechanical and biochemical signals involved in bone's adaptive response to loading. Exercise protocols, osteotomy procedures, loading of surgically implanted pins, and force application through the soft tissues are common approaches to alter the(More)