Browsing by Author "Brahmachary, Priyanka"

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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.
Metabolomic Profiles and Pathways in Osteoarthritic Human Cartilage: A Comparative Analysis with Healthy Cartilage
(MDPI AG, 2024-03) Welhaven, Hope D.; Welfley, Avery H.; Brahmachary, Priyanka; Bergstrom, Annika R.; Houske, Eden; Glimm, Matthew; Bothner, Brian; Hahn, Alyssa K.; June, Ronald K.
Osteoarthritis (OA) is a chronic joint disease with heterogenous metabolic pathology. To gain insight into OA-related metabolism, metabolite extracts from healthy (n = 11) and end-stage osteoarthritic cartilage (n = 35) were analyzed using liquid chromatography–mass spectrometry metabolomic profiling. Specific metabolites and metabolic pathways, including lipid and amino acid pathways, were differentially regulated in osteoarthritis-derived and healthy cartilage. The detected alterations in amino acids and lipids highlighted key differences in bioenergetic resources, matrix homeostasis, and mitochondrial alterations in OA-derived cartilage compared to healthy cartilage. Moreover, the metabolomic profiles of osteoarthritic cartilage separated into four distinct endotypes, highlighting the heterogenous nature of OA metabolism and the diverse landscape within the joint in patients. The results of this study demonstrate that human cartilage has distinct metabolomic profiles in healthy and end-stage OA patients. By taking a comprehensive approach to assess metabolic differences between healthy and osteoarthritic cartilage and within osteoarthritic cartilage alone, several metabolic pathways with distinct regulation patterns were detected. Additional investigation may lead to the identification of metabolites that may serve as valuable indicators of disease status or potential therapeutic targets.
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.
Metabolomic Profiling to Understand Chondrocyte Metabolism
(2021) 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.
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.