All Publications

  • Aging of Skeletal Stem Cells. Advances in geriatric medicine and research Butler, M. G., Ambrosi, T. H., Murphy, M. P., Chan, C. K. 2022; 4 (2)


    The skeletal system is generated and maintained by its progenitors, skeletal stem cells (SSCs), across the duration of life. Gradual changes associated with aging result in significant differences in functionality of SSCs. Declines in bone and cartilage production, increase of bone marrow adipose tissue, compositional changes of cellular microenvironments, and subsequent deterioration of external and internal structures culminate in the aged and weakened skeleton. The features and mechanisms of skeletal aging, and of its stem and progenitor cells in particular, are topics of recent investigation. The discovery of functionally homogeneous SSC populations with a defined cell surface phenotype has allowed for closer inspection of aging in terms of its effects on transcriptional regulation, cell function, and identity. Here, we review the aspects of SSC aging on both micro- and macroscopic levels. Up-to-date knowledge of SSC biology and aging is presented, and directions for future research and potential therapies are discussed. The realm of SSC-mediated bone aging remains an important component of global health and a necessary facet in our understanding of human aging.

    View details for DOI 10.20900/agmr20220006

    View details for PubMedID 36037035

  • Cross-species comparisons reveal resistance of human skeletal stem cells to inhibition by non-steroidal anti-inflammatory drugs. Frontiers in endocrinology Goodnough, L. H., Ambrosi, T. H., Steininger, H. M., Butler, M. G., Hoover, M. Y., Choo, H., Van Rysselberghe, N. L., Bellino, M. J., Bishop, J. A., Gardner, M. J., Chan, C. K. 2022; 13: 924927


    Fracture healing is highly dependent on an early inflammatory response in which prostaglandin production by cyclo-oxygenases (COX) plays a crucial role. Current patient analgesia regimens favor opioids over Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) since the latter have been implicated in delayed fracture healing. While animal studies broadly support a deleterious role of NSAID treatment to bone-regenerative processes, data for human fracture healing remains contradictory. In this study, we prospectively isolated mouse and human skeletal stem cells (SSCs) from fractures and compared the effect of various NSAIDs on their function. We found that osteochondrogenic differentiation of COX2-expressing mouse SSCs was impaired by NSAID treatment. In contrast, human SSCs (hSSC) downregulated COX2 expression during differentiation and showed impaired osteogenic capacity if COX2 was lentivirally overexpressed. Accordingly, short- and long-term treatment of hSSCs with non-selective and selective COX2 inhibitors did not affect colony forming ability, chondrogenic, and osteogenic differentiation potential in vitro. When hSSCs were transplanted ectopically into NSG mice treated with Indomethacin, graft mineralization was unaltered compared to vehicle injected mice. Thus, our results might contribute to understanding species-specific differences in NSAID sensitivity during fracture healing and support emerging clinical data which conflicts with other earlier observations that NSAID administration for post-operative analgesia for treatment of bone fractures are unsafe for patients.

    View details for DOI 10.3389/fendo.2022.924927

    View details for PubMedID 36093067