Browsing by Subject "Bone Formation"

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    The Emerging Role of Osteocytes in Cancer in Bone
    (Wiley, 2019-02-27) Atkinson, Emily G.; Delgado‐Calle, Jesús; Anatomy and Cell Biology, School of Medicine
    Advances in the last decade have established the osteocyte, the most abundant cell in bone, as a dynamic and multifunctional cell capable of controlling bone homeostasis by regulating the function of both osteoblasts and osteoclasts. In addition, accumulating evidence demonstrates that osteocyte function is altered in several skeletal disorders, and targeting osteocytes and their derived factors improves skeletal health. Despite the remarkable progress in our understanding of osteocyte biology, there has been a paucity of information regarding the role of osteocytes in the progression of cancer in bone. Exciting, recent discoveries suggest that tumor cells communicate with osteocytes to generate a microenvironment that supports the growth and survival of cancer cells and stimulates bone destruction. This review features these novel findings and discussions regarding the impact of chemotherapy on osteocyte function and the potential of targeting osteocytes for the treatment of cancer in bone. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.
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    Experimental and Computational Analysis of Dynamic Loading for Bone Formation
    (2013-11-12) Dodge, Todd Randall; Wallace, Joseph; Na, Sungsoo; Yokota, Hiroki, 1955-; Schild, John H.
    Bone is a dynamic tissue that is constantly remodeling to repair damage and strengthen regions exposed to loads during everyday activities. However, certain conditions, including long-term unloading of the skeleton, hormonal imbalances, and aging can disrupt the normal bone remodeling cycle and lead to low bone mass and osteoporosis, increasing risk of fracture. While numerous treatments for low bone mass have been devised, dynamic mechanical loading modalities, such as axial loading of long bones and lateral loading of joints, have recently been examined as potential methods of stimulating bone formation. The effectiveness of mechanical loading in strengthening bone is dependent both on the structural and geometric characteristics of the bone and the properties of the applied load. For instance, curvature in the structure of a bone causes bending and increased strain in response to an axial load, which may contribute to increased bone formation. In addition, frequency of the applied load has been determined to impact the degree of new bone formation; however, the mechanism behind this relationship remains unknown. In this thesis, the application of mechanical loading to treat osteoporotic conditions is examined and two questions are addressed: What role does the structural geometry of bone play in the mechanical damping of forces applied during loading? Does mechanical resonance enhance geometric effects, leading to localized areas of elevated bone formation dependent on loading frequency? Curvature in the structure of bone was hypothesized to enhance its damping ability and lead to increased bone formation through bending. In addition, loading at frequencies near the resonant frequencies of bone was predicted to cause increased bone formation, specifically in areas that experienced high principal strains due to localized displacements during resonant vibration. To test the hypothesis, mechanical loading experiments and simulations using finite element (FE) analysis were conducted to characterize the dynamic properties of bone. Results demonstrate that while surrounding joints contribute to the greatest portion of the damping capacity of the lower limb, bone absorbs a significant amount of energy through curvature-driven bending. In addition, results show that enhanced mechanical responses at loading frequencies near the resonant frequencies of bone may lead to increased bone formation in areas that experience the greatest principal strain during vibration. These findings demonstrate the potential therapeutic effects of mechanical loading in preventing costly osteoporotic fractures, and explore characteristics of bone that may lead to optimization of mechanical loading techniques. Further investigation of biomechanical properties of bone may lead to the prescribing of personalized mechanical loading treatments to treat osteoporotic diseases.