Biology subjects

Vahidi, G.

Publications and source records attributed to Vahidi, G..

5 recordsLinked to original sources

bioRxiv2024

High-fat diet exacerbates the loss of bone fracture toughness in aging for C57BL/6JN mice

The elderly are at increased risk of bone fracture and more often consume poor quality diets, such as high-fat diet (HFD). We hypothesized that HFD would exacerbate the loss of bone fracture resistance in aging. To test this hypothesis, we fed 5-month and 22-month C57BL/6JN mice of both sexes HFD or low-fat diet for 8 weeks. Aging and HFD lowered bone fracture toughness, while only aging reduced bone strength. At the tissue-scale, aging increased bone mineral maturity, while HFD altered bone mineralization and maturity as well as collagen structure. Cortical bone metabolism was also dysregulated with aging and HFD. Dysregulated pathways in aging and HFD were related to cellular function and viability, or glucose regulation, respectively. Aging with HFD also impacted osteoclast and adipocyte abundance and osteocyte viability. Together, these data demonstrate that HFD may exacerbate the loss of bone matrix quality and fracture resistance in aging.

bioengineering↗

bioRxiv2023

Aging decreases osteocyte lacunar-canalicular turnover in female C57BL/6 mice

Osteocytes engage in bone resorption and mineralization surrounding their expansive lacunar-canalicular system (LCS) through LCS turnover. However, fundamental questions persist about where, when, and how often osteocytes engage in LCS turnover and how these processes change with aging. Furthermore, whether LCS turnover depends on tissue strain remains unexplored. To address these questions, we utilized confocal scanning microscopy, immunohistochemistry, and scanning electron microscopy to characterize osteocyte LCS turnover in the cortical (mid-diaphysis) and cancellous (metaphysis) femurs from young (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 markers of bone resorption. The dynamics of LCS turnover were estimated from serial fluorochrome labeling, where each mouse was administered two labels between 2 days 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 LCS turnover dynamics in cancellous bone than in cortical bone. Lacunae with recent LCS turnover have larger lacunae in both age groups. The impacts of aging on LCS turnover also varies with cortical region of interest and intracortical location, suggesting a dependence on tissue strain. The impact of aging on decreasing LCS turnover may have significant implications for bone quality and mechanosensation. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=88 SRC="FIGDIR/small/571934v1_ufig1.gif" ALT="Figure 1"> View larger version (49K): org.highwire.dtl.DTLVardef@cbb7a9org.highwire.dtl.DTLVardef@86d667org.highwire.dtl.DTLVardef@660eb8org.highwire.dtl.DTLVardef@5062a6_HPS_FORMAT_FIGEXP M_FIG Graphical abstractOsteocyte participation in lacunar-canalicular system (LCS) mineralization is abundant in young mice but decreases with aging in both cortical and cancellous bone. Aging also reduces LCS bone resorption. Aging alters the relationship between LCS turnover and variation in cortical tissue strain. C_FIG

physiology↗

bioRxiv2022

The gut microbiome has sexually dimorphic effects on bone tissue energy metabolism and multiscale bone quality in C57BL/6J mice

The gut microbiome impacts bone mass, implying a disruption to bone homeostasis, yet significant uncertainty remains regarding the impacts of the gut microbiome on remodeling bone cells. The gut microbiome is thought to be essential for normal biomineralization, but the specific consequences of the absent gut microbiome on tissue mineralization and multiscale bone quality are not determined. We hypothesized that bone homeostasis and tissue-scale metabolism, tissue mineralization, and whole-bone biomechanics are altered in germ-free (GF) C57BL/6J mice. Further, because many characteristics of the gut microbiome are sexually dimorphic, we hypothesized that the gut microbiome would show important sex differences with regards to its impact on bone quality. Differences between GF and conventional mouse bone extended from bone tissue metabolism to whole bone biomechanics. Cortical bone tissue from male mice had a greater signature of amino acid metabolism whereas female cells had a greater signature of lipid metabolism. These sex differences were also present in GF mice and were indeed even more stark. GF increased cortical femur bone formation for both sexes and decreased bone resorption and osteoclast density only in females. GF similarly increased cortical femur tissue mineralization and altered collagen structure for both sexes but led to greater gains in distal femur trabecular microarchitecture for males. Whole femur strength was similarly increased with GF for both sexes, but males had a greater increase in modulus. GF did not impact fracture toughness for either sex. The altered bone quality with GF is multifactorial and is likely contributed to by differences in tissue-scale composition as well as lower cortical porosity. Together, these data demonstrate that the gut microbiome influences bone cells and multiscale bone quality, but that the specific relationships that underlie these effects to bone are different for females and males.

microbiology↗

bioRxiv2021

Perilacunar bone tissue exhibits sub-micrometer modulus gradation which depends on the recency of osteocyte bone formation

Osteocytes are capable of resorbing and replacing bone local to the lacunar-canalicular system (LCS remodeling). However, the impacts of these processes on perilacunar bone quality are not understood. It is well established that aging is associated with reduced whole-bone fracture resistance, reduced osteocyte viability, and truncated LCS geometries, but it remains unclear if aging changes perilacunar bone quality. In this study, we employed atomic force microscopy (AFM) to quantify sub-micrometer gradations from 2D maps surrounding osteocyte lacunae in young (5 mo) and aged (22 mo) female mice. AFM-mapped lacunae were also imaged with confocal laser scanning microscopy to determine which osteocytes had recently deposited bone as determined by the presence of fluorochrome labels. These assays allowed us to quantify gradations in nanoscale mechanical properties of bone-forming/non-bone-forming osteocytes in young and aged mice. This study reports for the first time that there are sub-micrometer gradations in modulus surrounding lacunae and that these gradations are dependent upon recent osteocyte bone formation. Perilacunar bone adjacent to bone-forming osteocytes demonstrated lower peak and bulk modulus values when compared to bone near non-bone-forming osteocytes from the same mouse. Bone-forming osteocytes also showed increased perilacunar modulus variability. Age reduced lacunar size but did not significant effect modulus gradation or variability. In general, lacunar morphology was not a strong predictor of modulus gradation patterns. These findings support the idea that lacunar-canalicular remodeling activity changes the material properties of surrounding bone tissue on a sub-micrometer scale. Therefore, conditions that affect osteocyte health have the potential to impact bone quality. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=62 SRC="FIGDIR/small/461298v1_ufig1.gif" ALT="Figure 1"> View larger version (29K): org.highwire.dtl.DTLVardef@1fe5a68org.highwire.dtl.DTLVardef@1e17e90org.highwire.dtl.DTLVardef@13c2e3corg.highwire.dtl.DTLVardef@1ff9f38_HPS_FORMAT_FIGEXP M_FIG C_FIG

physiology↗

bioRxiv2021

The mouse bone metabolome is sexually dimorphic and is associated with whole bone strength

Cortical bone quality, which is sexually dimorphic, depends on bone turnover and therefore the activities of remodeling bone cells. However, sex differences in cortical bone metabolism are not yet defined. Adding to the uncertainty about cortical bone metabolism, the metabolomes of whole bone, isolated cortical bone without marrow, and bone marrow have not been compared. We hypothesized that the metabolome of isolated cortical bone would be distinct from that of bone marrow and would reveal sex differences. Metabolite profiles from LC-MS of whole bone, isolated cortical bone, and bone marrow were generated from humeri from 20-week-old female C57Bl/6J mice. The cortical bone metabolomes were then compared for 20-week-old female and male C57Bl/6J mice. Femurs from male and female mice were evaluated for flexural material properties and were then categorized into bone strength groups. The metabolome of isolated cortical bone was distinct from both whole bone and bone marrow. We also found sex differences in the isolated cortical bone metabolome. Based on metabolite pathway analysis, females had higher lipid metabolism, and males had higher amino acid metabolism. High-strength bones, regardless of sex, had greater tryptophan and purine metabolism. For males, high strength bones had upregulated nucleotide metabolism, whereas lower strength bones had greater pentose phosphate pathway metabolism. Since the higher strength groups (females compared with males, high strength males compared with lower strength males) had higher serum CTX1/P1NP, we estimate that the metabolomic signature of bone strength in our study at least partially reflects differences in bone turnover. These data provide novel insight into bone bioenergetics and the sexual dimorphic nature of bone material properties in C57Bl/6 mice.

cell biology↗