Browsing by Author "Vahidi, Ghazal"

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Aging decreases osteocyte peri-lacunar-canalicular system turnover in female C57BL/6JN mice
(Elsevier BV, 2024-09) Vahidi, Ghazal; Boone, C.; Hoffman, F. O.; Heveran, Chelsea M.
Osteocytes engage in bone resorption and mineralization surrounding their expansive lacunar-canalicular system (LCS) through peri-LCS turnover. However, fundamental questions persist about where, when, and how often osteocytes engage in peri-LCS turnover and how these processes change with aging. Furthermore, whether peri-LCS turnover is associated with natural variation in cortical tissue strain remains unexplored. To address these questions, we utilized confocal scanning microscopy, immunohistochemistry, and scanning electron microscopy to characterize osteocyte peri-LCS turnover in the cortical (mid-diaphysis) and cancellous (metaphysis) regions of femurs from young adult (5 mo) and early-old-age (22 mo) female C57BL/6JN mice. LCS bone mineralization was measured by the presence of perilacunar fluorochrome labels. LCS bone resorption was measured by immunohistochemical marker of bone resorption. The dynamics of peri-LCS turnover were estimated from serial fluorochrome labeling, where each mouse was administered two labels between 2 and 16 days before euthanasia. Osteocyte participation in mineralizing their surroundings is highly abundant in both cortical and cancellous bone of young adult mice but significantly decreases with aging. LCS bone resorption also decreases with aging. Aging has a greater impact on peri-LCS turnover dynamics in cancellous bone than in cortical bone. Lacunae with recent peri-LCS turnover are larger in both age groups. While peri-LCS turnover is associated with variation in tissue strain between cortical quadrants and intracortical location for 22 mo mice, these associations were not seen for 5 mo mice. The impact of aging on decreasing peri-LCS turnover may have significant implications for bone quality and mechanosensation.
Germ‐Free C57BL/6 Mice Have Increased Bone Mass and Altered Matrix Properties but Not Decreased Bone Fracture Resistance
(Wiley, 2023-08) Vahidi, Ghazal; Moody, Maya; Welhave, Hope D.; Davidson, Leah; Rezaee, Taraneh; Behzad, Ramina; Karim, Lamya; Roggenbeck, Barbara A.; Walk, Seth T.; Martin, Stephen A.; June, Ronald K.; Heveran, Chelsea M.
The gut microbiome impacts bone mass, which implies a disruption to bone homeostasis. However, it is not yet clear how the gut microbiome affects the regulation of bone mass and bone quality. We hypothesized that germ-free (GF) mice have increased bone mass and decreased bone toughness compared with conventionally housed mice. We tested this hypothesis using adult (20- to 21-week-old) C57BL/6J GF and conventionally raised female and male mice (n = 6–10/group). Trabecular microarchitecture and cortical geometry were measured from micro–CT of the femur distal metaphysis and cortical midshaft. Whole-femur strength and estimated material properties were measured using three-point bending and notched fracture toughness. Bone matrix properties were measured for the cortical femur by quantitative back-scattered electron imaging and nanoindentation, and, for the humerus, by Raman spectroscopy and fluorescent advanced glycation end product (fAGE) assay. Shifts in cortical tissue metabolism were measured from the contralateral humerus. GF mice had reduced bone resorption, increased trabecular bone microarchitecture, increased tissue strength and decreased whole-bone strength that was not explained by differences in bone size, increased tissue mineralization and fAGEs, and altered collagen structure that did not decrease fracture toughness. We observed several sex differences in GF mice, most notably for bone tissue metabolism. Male GF mice had a greater signature of amino acid metabolism, and female GF mice had a greater signature of lipid metabolism, exceeding the metabolic sex differences of the conventional mice. Together, these data demonstrate that the GF state in C57BL/6J mice alters bone mass and matrix properties but does not decrease bone fracture resistance. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
Lacunar-canalicular bone remodeling: Impacts on bone quality and tools for assessment
(2021-02) Vahidi, Ghazal; Rux, Caleb; Sherk, Vanessa D.; Heveran, Chelsea M.
Osteocytes can resorb as well as replace bone adjacent to the expansive lacunar-canalicular system (LCS). Suppressed LCS remodeling decreases bone fracture toughness, but it is unclear how altered LCS remodeling impacts bone quality. The first goal of this review is to assess how LCS remodeling impacts LCS morphology as well as the composition and mechanical properties of surrounding bone tissue. The second goal is to compare tools available for the assessment of bone quality at length-scales that are physiologically-relevant to LCS remodeling. We find that changes to LCS morphology occur in response to a variety of physiological conditions and diseases and can be classified in two general phenotypes. In the ‘aging phenotype’, seen in aging and in some disuse models, the LCS is truncated and osteocytes apoptosis is increased. In the ‘osteocytic osteolysis’ phenotype, which is adaptive in some physiological settings and possibly maladaptive in others, the LCS enlarges and osteocytes generally maintain viability. Bone composition and mechanical properties vary near the osteocyte and change with at least some conditions that alter LCS morphology. However, few studies have evaluated bone composition and mechanical properties close to the LCS and so the impacts of LCS remodeling phenotypes on bone tissue quality are still undetermined. We summarize the current understanding of how LCS remodeling impacts LCS morphology, tissue-scale bone composition and mechanical properties, and whole-bone material properties. Tools are compared for assessing tissue-scale bone properties, as well as the resolution, advantages, and limitations of these techniques.