Browsing by Author "Heveran, Chelsea M."

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Aging alters the subchondral bone response 7 days after noninvasive traumatic joint injury in C57BL/6JN mice
(Wiley, 2024) Dauenhauer, Lexia A.; Hislop, Brady D.; Brahmachary, Priyanka; Devine, Connor; Gibbs, Dustin; June, Ronald K.; Heveran, Chelsea M.
Posttraumatic osteoarthritis (PTOA) commonly develops following anterior cruciate ligament (ACL) injuries, affecting around 50% of individuals within 10–20 years. Recent studies have highlighted early changes in subchondral bone structure after ACL injury in adolescent or young adult mice, which could contribute to the development of PTOA. However, ACL injuries do not only occur early in life. Middle-aged and older patients also experience ACL injuries and PTOA, but whether the aged subchondral bone also responds rapidly to injury is unknown. This study utilized a noninvasive, single overload mouse injury model to assess subchondral bone microarchitecture, turnover, and material properties in both young adults (5 months) and early old age (22 months) female C57BL/6JN mice at 7 days after injury. Mice underwent either joint injury (i.e., produces ACL tears) or sham injury procedures on both the loaded and contralateral limbs, allowing evaluation of the impacts of injury versus loading. The subchondral bone response to ACL injury is distinct for young adult and aged mice. While 5-month mice show subchondral bone loss and increased bone resorption postinjury, 22-month mice did not show loss of bone structure and had lower bone resorption. Subchondral bone plate modulus increased with age, but not with injury. Both ages of mice showed several bone measures were altered in the contralateral limb, demonstrating the systemic skeletal response to joint injury. These data motivate further investigation to discern how osteochondral tissues differently respond to injury in aging, such that diagnostics and treatments can be refined for these demographics.
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.
Biomineralization of Plastic Waste to Improve the Strength of Plastic-Reinforced Cement Mortar
(2021-04) Kane, Seth; Thane, Abby; Espinal, Michael; Lunday, Kendra; Armagan, Hakan; Phillips, Adrienne J.; Heveran, Chelsea M.; Ryan, Cecily A.
The development of methods to reuse large volumes of plastic waste is essential to curb the environmental impact of plastic pollution. Plastic-reinforced cementitious materials (PRCs), such as plastic-reinforced mortar (PRM), may be potential avenues to productively use large quantities of low-value plastic waste. However, poor bonding between the plastic and cement matrix reduces the strength of PRCs, limiting its viable applications. In this study, calcium carbonate biomineralization techniques were applied to coat plastic waste and improved the compressive strength of PRM. Two biomineralization treatments were examined: enzymatically induced calcium carbonate precipitation (EICP) and microbially induced calcium carbonate precipitation (MICP). MICP treatment of polyethylene terephthalate (PET) resulted in PRMs with compressive strengths similar to that of plastic-free mortar and higher than the compressive strengths of PRMs with untreated or EICP-treated PET. Based on the results of this study, MICP was used to treat hard-to-recycle types 3–7 plastic waste. No plastics investigated in this study inhibited the MICP process. PRM samples with 5% MICP-treated polyvinyl chloride (PVC) and mixed type 3–7 plastic had compressive strengths similar to plastic-free mortar. These results indicate that MICP treatment can improve PRM strength and that MICP-treated PRM shows promise as a method to reuse plastic waste.
Carpenter bee thorax vibration and force generation inform pollen release mechanisms during floral buzzing
(Springer Nature, 2022-08) Jankausk, Mark; Casey, Cailin; Heveran, Chelsea M.; Busby, M. Kathryn; Buchmann, Stephen
Approximately 10% of flowering plant species conceal their pollen within tube-like poricidal anthers. Bees extract pollen from poricidal anthers via floral buzzing, a behavior during which they apply cyclic forces by biting the anther and rapidly contracting their flight muscles. The success of pollen extraction during floral buzzing relies on the direction and magnitude of the forces applied by the bees, yet these forces and forcing directions have not been previously quantified. In this work, we developed an experiment to simultaneously measure the directional forces and thorax kinematics produced by carpenter bees (Xylocopa californica) during defensive buzzing, a behavior regulated by similar physiological mechanisms as floral buzzing. We found that the buzzing frequencies averaged about 130 Hz and were highly variable within individuals. Force amplitudes were on average 170 mN, but at times reached nearly 500 mN. These forces were 30–80 times greater than the weight of the bees tested. The two largest forces occurred within a plane formed by the bees’ flight muscles. Force amplitudes were moderately correlated with thorax displacement, velocity and acceleration amplitudes but only weakly correlated with buzzing frequency. Linear models developed through this work provide a mechanism to estimate forces produced during non-flight behaviors based on thorax kinematic measurements in carpenter bees. Based on the buzzing frequencies, individual bee’s capacity to vary buzz frequency and predominant forcing directions, we hypothesize that carpenter bees leverage vibration amplification to increase the deformation of poricidal anthers, and hence the amount of pollen ejected.
Carpenter bee thorax vibration and force generation inform pollen release mechanisms during floral buzzing
(Springer Science and Business Media LLC, 2022-08) Jankauski, Mark; Casey, Cailin; Heveran, Chelsea M.; Busby, M. Kathryn; Buchmann, Stephen
Approximately 10% of flowering plant species conceal their pollen within tube-like poricidal anthers. Bees extract pollen from poricidal anthers via floral buzzing, a behavior during which they apply cyclic forces by biting the anther and rapidly contracting their flight muscles. The success of pollen extraction during floral buzzing relies on the direction and magnitude of the forces applied by the bees, yet these forces and forcing directions have not been previously quantified. In this work, we developed an experiment to simultaneously measure the directional forces and thorax kinematics produced by carpenter bees (Xylocopa californica) during defensive buzzing, a behavior regulated by similar physiological mechanisms as floral buzzing. We found that the buzzing frequencies averaged about 130 Hz and were highly variable within individuals. Force amplitudes were on average 170 mN, but at times reached nearly 500 mN. These forces were 30–80 times greater than the weight of the bees tested. The two largest forces occurred within a plane formed by the bees’ flight muscles. Force amplitudes were moderately correlated with thorax displacement, velocity and acceleration amplitudes but only weakly correlated with buzzing frequency. Linear models developed through this work provide a mechanism to estimate forces produced during non-flight behaviors based on thorax kinematic measurements in carpenter bees. Based on the buzzing frequencies, individual bee’s capacity to vary buzz frequency and predominant forcing directions, we hypothesize that carpenter bees leverage vibration amplification to increase the deformation of poricidal anthers, and hence the amount of pollen ejected.
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.
Osteochondral fluid transport in an ex vivo system
(Elsevier BV, 2024-04) Hislop, Brady David; Mercer, Ara K.; Whitley, Alexandria G.; Myers, Erik P.; Mackin, Marie; Heveran, Chelsea M.; June, Ronald K.
Objective: Alterations to bone-to-cartilage fluid transport may contribute to the development of osteoarthritis (OA). Larger biological molecules in bone may transport from bone-to-cartilage (e.g., insulin, 5 kDa). However, many questions remain about fluid transport between these tissues. The objectives of this study were to (1) test for diffusion of 3 kDa molecular tracers from bone-to-cartilage and (2) assess potential differences in bone-to-cartilage fluid transport between different loading conditions. Design: Osteochondral cores extracted from bovine femurs (N = 10 femurs, 10 cores/femur) were subjected to either no-load (i.e., pure diffusion), pre-load only, or cyclic compression (5 ± 2% or 10 ± 2% strain) in a two-chamber bioreactor. The bone was placed into the bone compartment followed by a 3 kDa dextran tracer, and tracer concentrations in the cartilage compartment were measured every 5 min for 120 min. Tracer concentrations were analyzed for differences in beginning, peak, and equilibrium concentrations, loading effects, and time-to-peak tracer concentration. Results: Peak tracer concentration in the cartilage compartment was significantly higher compared to the beginning and equilibrium tracer concentrations. Cartilage-compartment tracer concentration and maximum fluorescent intensity were influenced by strain magnitude. No time-to-peak relationship was found between strain magnitudes and cartilage-compartment tracer concentration. Conclusion: This study shows that bone-to-cartilage fluid transport occurs with 3 kDa dextran molecules. These are larger molecules to move between bone and cartilage than previously reported. Further, these results demonstrate the potential impact of cyclic compression on osteochondral fluid transport. Determining the baseline osteochondral fluid transport in healthy tissues is crucial to elucidating the mechanisms OA pathology.
Rapamycin does not alter bone microarchitecture or material properties quality in young-adult and aged female C57BL/6 mice
(Oxford University Press, 2024-01) Devine, Connor C.; Brown, Kenna C.; Paton, Kat O.; Heveran, Chelsea M.; Martin, Stephen A.
Advancing age is the strongest risk factor for osteoporosis and skeletal fragility. Rapamycin is an FDA-approved immunosuppressant that inhibits the mechanistic target of rapamycin (mTOR) complex, extends lifespan, and protects against aging-related diseases in multiple species; however, the impact of rapamycin on skeletal tissue is incompletely understood. We evaluated the effects of a short-term, low-dosage, interval rapamycin treatment on bone microarchitecture and strength in young-adult (3 mo old) and aged female (20 mo old) C57BL/6 mice. Rapamycin (2 mg/kg body mass) was administered via intraperitoneal injection 1×/5 d for a duration of 8 wk; this treatment regimen has been shown to induce geroprotective effects while minimizing the side effects associated with higher rapamycin dosages and/or more frequent or prolonged delivery schedules. Aged femurs exhibited lower cancellous bone mineral density, volume, trabecular connectivity density and number, higher trabecular thickness and spacing, and lower cortical thickness compared to young-adult mice. Rapamycin had no impact on assessed microCT parameters. Flexural testing of the femur revealed that both yield strength and ultimate strength were lower in aged mice compared to young-adult mice. There were no effects of rapamycin on these or other measures of bone biomechanics. Age, but not rapamycin, altered local and global measures of bone turnover. These data demonstrate that short-term, low-dosage interval rapamycin treatment does not negatively or positively impact the skeleton of young-adult and aged mice.
Subchondral bone structure and synovial fluid metabolism are altered in injured and contralateral limbs 7 days after non-invasive joint injury in skeletally-mature C57BL/6 mice
(Elsevier BV, 2022-12) Hislop, B. D.; Devine, C.; June, R. K.; Heveran, Chelsea M.
Objective. Post-traumatic osteoarthritis (PTOA) commonly develops after ACL injury, but early changes to the joint soon after injury are insufficiently understood. The objectives of this study were (1) evaluate the response of subchondral bone tissue modulus to joint injury and (2) identify which bone structural, material, and metabolic outcomes are local (i.e., injured joint only) or systemic (i.e., injured and contralateral-to-injured). Design. Female C57Bl∖6N mice (19 weeks at injury) underwent tibial compression overload to simulate ACL injury (n = 8) or a small pre-load (n = 8). Synovial fluid was harvested at euthanasia 7 days later for metabolomic profiling. Bone outcomes included epiphyseal and SCB microarchitecture, SCB nanoindentation modulus, SCB formation rate, and osteoclast number density. Results. Injury decreased epiphyseal bone volume fraction ([-5.29, −1.38%], P = 0.0016) and decreased SCB thickness for injured vs sham-injured limbs ([2.2, 31.4 μm], P = 0.017)). Epiphyseal bone loss commonly occurred for contralateral-to-injured limbs. There was not sufficient evidence to conclude that SCB modulus changes with injury. Metabolomic analyses revealed dysregulated synovial fluid metabolism with joint injury but that many metabolic pathways are shared between injured and contralateral-to-injured limbs.Conclusion. This study demonstrates rapid changes to bone structure and synovial fluid metabolism after injury with the potential for influencing the progression to PTOA. These changes are often evidenced in the contralateral-to-injured limb, indicating that systemic musculoskeletal responses to joint injury should not be overlooked.
Subchondral bone structure and synovial fluid metabolism are altered in injured and contralateral limbs 7 days after non-invasive joint injury in skeletally-mature C57BL/6 mice
(Elsevier BV, 2022-12) Hislop, B.D.; Devine, C.; June, R.K.; Heveran, Chelsea M.
Objective: Post-traumatic osteoarthritis (PTOA) commonly develops after ACL injury, but early changes to the joint soon after injury are insufficiently understood. The objectives of this study were (1) evaluate the response of subchondral bone tissue modulus to joint injury and (2) identify which bone structural, material, and metabolic outcomes are local (i.e., injured joint only) or systemic (i.e., injured and contralateral-to-injured). Design: Female C57Bl\6N mice (19 weeks at injury) underwent tibial compression overload to simulate ACL injury (n ¼ 8) or a small pre-load (n ¼ 8). Synovial fluid was harvested at euthanasia 7 days later for metabolomic profiling. Bone outcomes included epiphyseal and SCB microarchitecture, SCB nano- indentation modulus, SCB formation rate, and osteoclast number density. Results: Injury decreased epiphyseal bone volume fraction ([-5.29, 1.38%], P ¼ 0.0016) and decreased SCB thickness for injured vs sham-injured limbs ([2.2, 31.4 mm], P ¼ 0.017)). Epiphyseal bone loss commonly occurred for contralateral-to-injured limbs. There was not sufficient evidence to conclude that SCB modulus changes with injury. Metabolomic analyses revealed dysregulated synovial fluid metabolism with joint injury but that many metabolic pathways are shared between injured and contralateral-to-injured limbs. Conclusion: This study demonstrates rapid changes to bone structure and synovial fluid metabolism after injury with the potential for influencing the progression to PTOA. These changes are often evidenced in the contralateral-to-injured limb, indicating that systemic musculoskeletal responses to joint injury should not be overlooked.