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Osteoporosis is a major skeletal disease with low bone mineral density, which leads to an increased risk of bone fracture. Salubrinal is a synthetic chemical that inhibits dephosphorylation of eukaryotic translation initiation factor 2 alpha (eIF2α) in response to endoplasmic reticulum (ER) stress. To understand possible linkage of osteoporosis to ER stress, we employed an unloading mouse model and...
Osteonecrosis of the femoral head is a serious orthopedic problem. Moderate loads with knee loading promote bone formation, but their effects on osteonecrosis have not been investigated. Using a rat model, we examined a hypothesis that knee loading enhances vessel remodeling and bone healing through the modulation of the fate of bone marrow-derived cells. In this study, osteonecrosis was induced by...
Healing of bone wounds is sensitive to various environmental stimuli. Using knee loading, which has been shown to stimulate bone formation in mouse femora and tibiae, we addressed a question: Does knee loading accelerate a closure of open wounds in a femur neck? A surgical wound (0.5mm in diameter) was generated at the femur neck in the left and right femora of C57/BL/6 female mice, and knee loading...
To assess the influence of high extracellular glucose levels on the osteogenic differentiation of bone marrow stromal cells (BMSCs) and to determine if Sonic hedgehog (Shh) protein can alleviate those effects. BMSCs were incubated with NG (normal glucose), NG+Shh (200 ng/ml Shh in normal glucose), NG+Shh+Gan (200 ng/ml Shh and 5 μmol/L GANT61 in normal glucose), HG (high glucose), HG+Shh (200 ng/ml...
Joint loading is a recently developed loading modality that induces anabolic responses by lateral loads applied to a synovial joint such as an elbow and a knee. The present study extended this loading modality to an ankle and addressed a question: does ankle loading promote bone formation in the tibia? If so, what signaling pathways are involved in the anabolic responses? Using C57BL/6 female mice...
Zfp521, a 30 C2H2 Kruppel-like zinc finger protein, is expressed at high levels at the periphery of early mesenchymal condensations prefiguring skeletal elements and in all developing bones in the perichondrium and periosteum, in osteoblast precursors and osteocytes, and in chondroblast precursors and growth plate prehypertrophic chondrocytes. Zfp521 expression in cultured mesenchymal cells is decreased...
Loads applied directly to the knee (knee loading) have recently been demonstrated to induce anabolic responses in femoral and tibial cortical bone. In order to examine the potential role of intramedullary pressure in generating those knee loading responses, we investigated the effects of drilling surgical holes that penetrated into the tibial medullary cavity and thereby modulated pressure alteration...
Dynamic mechanical loads have been known to stimulate bone formation. Many biophysical factors such as number of daily loading cycles, bone strain, strain-induced interstitial fluid flow, molecular transport, and modulation of intramedullary pressure have been considered as potential mediators in mechanotransduction of bone. Using a knee loading modality that enhances anabolic responses in mouse hindlimb,...
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