College of Engineering

Permanent URI for this communityhttps://scholarworks.montana.edu/handle/1/27

The College of Engineering at Montana State University will serve the State of Montana and the nation by fostering lifelong learning, integrating learning and discovery, developing and sharing technical expertise, and empowering students to be tomorrow's leaders.

Browse

Search Results

Now showing 1 - 10 of 23

Unraveling sex-specific risks of knee osteoarthritis before menopause: Do sex differences start early in life?
(Elsevier BV, 2024-05) Hernández, Paula; Bradford, John; Brahmachary, Priyanka; Ulman, Sophia; Robinson, Jennifer L.; June, Ronald K.; Cucchiarini, Magali
Objective. Sufficient evidence within the past two decades have shown that osteoarthritis (OA) has a sex-specific component. However, efforts to reveal the biological causes of this disparity have emerged more gradually. In this narrative review, we discuss anatomical differences within the knee, incidence of injuries in youth sports, and metabolic factors that present early in life (childhood and early adulthood) that can contribute to a higher risk of OA in females. Design. We compiled clinical data from multiple tissues within the knee joint—since OA is a whole joint disorder—aiming to reveal relevant factors behind the sex differences from different perspectives. Results. The data gathered in this review indicate that sex differences in articular cartilage, meniscus, and anterior cruciate ligament are detected as early as childhood and are not only explained by sex hormones. Aiming to unveil the biological causes of the uneven sex-specific risks for knee OA, we review the current knowledge of sex differences mostly in young, but also including old populations, from the perspective of (i) human anatomy in both healthy and pathological conditions, (ii) physical activity and response to injury, and (iii) metabolic signatures. Conclusions. We propose that to close the gap in health disparities, and specifically regarding OA, we should address sex-specific anatomic, biologic, and metabolic factors at early stages in life, as a way to prevent the higher severity and incidence of OA in women later in life.
Heat conduction simulation of chondrocyte-embedded agarose gels suggests negligible impact of viscoelastic dissipation on temperature change
(Elsevier BV, 2024-09) Myers, Erik; Piazza, Molly; Owkes, Mark; June, Ronald K.
Agarose is commonly used for 3D cell culture and to mimic the stiffness of the pericellular matrix of articular chondrocytes. Although it is known that both temperature and mechanical stimulation affect the metabolism of chondrocytes, little is known about the thermal properties of agarose hydrogels. Thermal properties of agarose are needed to analyze potential heat production by chondrocytes induced by various experimental stimuli (carbon source, cyclical compression, etc). Utilizing ASTM C177, a custom-built thermal conductivity measuring device was constructed and used to calculate the thermal conductivity of 4.5 % low gelling temperature agarose hydrogels. Additionally, Differential Scanning Calorimetry was used to calculate the specific heat capacity of the agarose hydrogels. Testing of chondrocyte-embedded agarose hydrogels commonly occurs in Phosphate-Buffered Saline (PBS), and thermal analysis requires the free convection coefficient of PBS. This was calculated using a 2D heat conduction simulation within MATLAB in tandem with experimental data collected for known boundary and initial conditions. The specific heat capacity and thermal conductivity of 4.5 % agarose hydrogels was calculated to be 2.85 J/g°C and 0.121 W/mK, respectively. The free convection coefficient of PBS was calculated to be 1000.1 W/m2K. The values of specific heat capacity and thermal conductivity for agarose are similar to the reported values for articular cartilage, which are 3.20 J/g°C and 0.21 W/mK (Moghadam, et al. 2014). These data show that cyclical loading of hydrogel samples with these thermal properties will result in negligible temperature increases. This suggests that in addition to 4.5 % agarose hydrogels mimicking the physiological stiffness of the cartilage PCM, they can also mimic the thermal properties of articular cartilage for in vitro studies.
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.
Unraveling sex-specific risks of knee osteoarthritis before menopause: Do sex differences start early in life?
(Elsevier BV, 2024-05) Hernandez, Paula A.; Churchill Bradford, John; Brahmachary, Priyanka; Ulman, Sophia; Robinson, Jennifer L.; June, Ronald K.; Cucchiarini, Magali
Objective. Sufficient evidence within the past two decades have shown that osteoarthritis (OA) has a sex-specific component. However, efforts to reveal the biological causes of this disparity have emerged more gradually. In this narrative review, we discuss anatomical differences within the knee, incidence of injuries in youth sports, and metabolic factors that present early in life (childhood and early adulthood) that can contribute to a higher risk of OA in females. Design. We compiled clinical data from multiple tissues within the knee joint—since OA is a whole joint disorder—aiming to reveal relevant factors behind the sex differences from different perspectives. Results. The data gathered in this review indicate that sex differences in articular cartilage, meniscus, and anterior cruciate ligament are detected as early as childhood and are not only explained by sex hormones. Aiming to unveil the biological causes of the uneven sex-specific risks for knee OA, we review the current knowledge of sex differences mostly in young, but also including old populations, from the perspective of (i) human anatomy in both healthy and pathological conditions, (ii) physical activity and response to injury, and (iii) metabolic signatures. Conclusions. We propose that to close the gap in health disparities, and specifically regarding OA, we should address sex-specific anatomic, biologic, and metabolic factors at early stages in life, as a way to prevent the higher severity and incidence of OA in women later in life.
Evolution and advancements in genomics and epigenomics in OA research: How far we have come
(Elsevier BV, 2024-02) Ramos, Yolande F. M.; Rice, Sarah J.; Ali, Shabana Amanda; Pastrello, Chiara; Jurisica, Igor; Farooq Rai, Muhammad; Collins, Kelsey H.; Lang, Annemarie; Maerz, Tristan; Geurts, Jeroen; Ruiz Romero, Cristina; June, Ronald K.; Appleton, C. Thomas; Rockel, Jason S.; Kapoor, Mohit
Objective. Osteoarthritis (OA) is the most prevalent musculoskeletal disease affecting articulating joint tissues, resulting in local and systemic changes that contribute to increased pain and reduced function. Diverse technological advancements have culminated in the advent of high throughput “omic” technologies, enabling identification of comprehensive changes in molecular mediators associated with the disease. Amongst these technologies, genomics and epigenomics – including methylomics and miRNomics, have emerged as important tools to aid our biological understanding of disease. Design. In this narrative review, we selected articles discussing advancements and applications of these technologies to OA biology and pathology. We discuss how genomics, deoxyribonucleic acid (DNA) methylomics, and miRNomics have uncovered disease-related molecular markers in the local and systemic tissues or fluids of OA patients. Results. Genomics investigations into the genetic links of OA, including using genome-wide association studies, have evolved to identify 100+ genetic susceptibility markers of OA. Epigenomic investigations of gene methylation status have identified the importance of methylation to OA-related catabolic gene expression. Furthermore, miRNomic studies have identified key microRNA signatures in various tissues and fluids related to OA disease. Conclusions. Sharing of standardized, well-annotated omic datasets in curated repositories will be key to enhancing statistical power to detect smaller and targetable changes in the biological signatures underlying OA pathogenesis. Additionally, continued technological developments and analysis methods, including using computational molecular and regulatory networks, are likely to facilitate improved detection of disease-relevant targets, in-turn, supporting precision medicine approaches and new treatment strategies for OA.
Three Decades of Advancements in Osteoarthritis Research: Insights from Transcriptomic, Proteomic, and Metabolomic Studies
(Elsevier BV, 2023-12) Farooq Rai, Muhammad; Collins, Kelsey H.; Lang, Annemarie; Maerz, Tristan; Geurts, Jeroen; Ruiz-Romero, Cristina; June, Ronald K.; Ramos, Yolande; Rice, Sarah J.; Ali, Shabana Amanda; Pastrello, Chiara; Jurisica, Igor; Appleton, C. Thomas; Rockel, Jason S.; Kapoor, Mohit
Objective. Osteoarthritis (OA) is a complex disease involving contributions from both local joint tissues and systemic sources. Patient characteristics, encompassing sociodemographic and clinical variables, are intricately linked with OA rendering its understanding challenging. Technological advancements have allowed for a comprehensive analysis of transcripts, proteomes and metabolomes in OA tissues/fluids through omic analyses. The objective of this review is to highlight the advancements achieved by omic studies in enhancing our understanding of OA pathogenesis over the last three decades. Design. We conducted an extensive literature search focusing on transcriptomics, proteomics and metabolomics within the context of OA. Specifically, we explore how these technologies have identified individual transcripts, proteins, and metabolites, as well as distinctive endotype signatures from various body tissues or fluids of OA patients, including insights at the single-cell level, to advance our understanding of this highly complex disease. Results. Omic studies reveal the description of numerous individual molecules and molecular patterns within OA-associated tissues and fluids. This includes the identification of specific cell (sub)types and associated pathways that contribute to disease mechanisms. However, there remains a necessity to further advance these technologies to delineate the spatial organization of cellular subtypes and molecular patterns within OA-afflicted tissues. Conclusions. Leveraging a multi-omics approach that integrates datasets from diverse molecular detection technologies, combined with patients’ clinical and sociodemographic features, and molecular and regulatory networks, holds promise for identifying unique patient endophenotypes. This holistic approach can illuminate the heterogeneity among OA patients and, in turn, facilitate the development of tailored therapeutic interventions.
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).
Pericellular Matrix Formation and Atomic Force Microscopy of Single Primary Human Chondrocytes Cultured in Alginate Microgels
(Wiley, 2023-09) Fredrikson, Jacob P.; Brahmachary, Priyanka P.; June, Ronald K.; Cox, Lewis M.; Chang, Connie B.
One of the main components of articular cartilage is the chondrocyte's pericellular matrix (PCM), which is critical for regulating mechanotransduction, biochemical cues, and healthy cartilage development. Here, individual primary human chondrocytes (PHC) are encapsulated and cultured in 50 µm diameter alginate microgels using drop-based microfluidics. This unique culturing method enables PCM formation and manipulation of individual cells. Over ten days, matrix formation is observed using autofluorescence imaging, and the elastic moduli of isolated cells are measured using AFM. Matrix production and elastic modulus increase are observed for the chondrons cultured in microgels. Furthermore, the elastic modulus of cells grown in microgels increases ≈ten-fold over ten days, nearly reaching the elastic modulus of in vivo PCM. The AFM data is further analyzed using a Gaussian mixture model and shows that the population of PHCs grown in microgels exhibit two distinct populations with elastic moduli averaging 9.0 and 38.0 kPa. Overall, this work shows that microgels provide an excellent culture platform for the growth and isolation of PHCs, enabling PCM formation that is mechanically similar to native PCM. The microgel culture platform presented here has the potential to revolutionize cartilage regeneration procedures through the inclusion of in vitro developed PCM.
Sex-specific effects of calving season on joint health and biomarkers in Montana ranchers
(Springer Science and Business Media LLC, 2023-01) Thompson, Matthew A.; Martin, Stephen A.; Hislop, Brady D.; Younkin, Roubie; Andrews, Tara M.; Miller, Kaleena; June, Ronald K.; Adams, Erik S.
Background. Agricultural workers have a higher incidence of osteoarthritis (OA), but the etiology behind this phenomenon is unclear. Calving season, which occurs in mid- to late-winter for ranchers, includes physical conditions that may elevate OA risk. Our primary aim was to determine whether OA biomarkers are elevated at the peak of calving season compared to pre-season, and to compare these data with joint health survey information from the subjects. Our secondary aim was to detect biomarker differences between male and female ranchers. Methods. During collection periods before and during calving season, male (n = 28) and female (n = 10) ranchers completed joint health surveys and provided samples of blood, urine, and saliva for biomarker analysis. Statistical analyses examined associations between mean biomarker levels and survey predictors. Ensemble cluster analysis identified groups having unique biomarker profiles. Results. The number of calvings performed by each rancher positively correlated with plasma IL-6, serum hyaluronic acid (HA) and urinary CTX-I. Thiobarbituric acid reactive substances (TBARS), a marker of oxidative stress, was significantly higher during calving season than pre-season and was also correlated with ranchers having more months per year of joint pain. We found evidence of sexual dimorphism in the biomarkers among the ranchers, with leptin being elevated and matrix metalloproteinase-3 diminished in female ranchers. The opposite was detected in males. WOMAC score was positively associated with multiple biomarkers: IL-6, IL-2, HA, leptin, C2C, asymmetric dimethylarginine, and CTX-I. These biomarkers represent enzymatic degradation, inflammation, products of joint destruction, and OA severity. Conclusions. The positive association between number of calvings performed by each rancher (workload) and both inflammatory and joint tissue catabolism biomarkers establishes that calving season is a risk factor for OA in Montana ranchers. Consistent with the literature, we found important sex differences in OA biomarkers, with female ranchers showing elevated leptin, whereas males showed elevated MMP-3.
Metabolomic Profiling to Understand Chondrocyte Metabolism
(Springer Nature, 2022-11) Brahmachary, Priyanka; Welhaven, Hope D.; June, Ronald K.
Metabolism has long been recognized as a critical physiological process necessary to maintain homeostasis in all types of cells including the chondrocytes of articular cartilage. Alterations in metabolism in disease and metabolic adaptation to physiological stimuli such as mechanical loading are increasingly recognized as important for understanding musculoskeletal systems such as synovial joints. Metabolomics is an emerging technique that allows quantitative measurement of thousands of small molecule metabolites that serve as both products and reactants to myriad reactions of cellular biochemistry. This protocol describes procedures to perform metabolomic profiling on chondrocytes and other tissues and fluids within the synovial joint.

College of Engineering

Browse

Filters

Settings

Sort By

Results per page

Search Results