Search

The biology of bone healing is a rapidly developing science. Advances in transgenic and gene‐targeted mice have enabled tissue and cell‐specific investigations of skeletal regeneration. As an example, only recently has it been recognized that chondrocytes convert to osteoblasts during healing bone, and only several years prior, seminal publications reported definitively that the primary tissues contributing bone forming cells during regeneration were the periosteum and endosteum. While genetically modified animals offer incredible insights into the temporal and spatial importance of various gene products, the complexity and rapidity of healing—coupled with the heterogeneity of animal models—renders studies of regenerative biology challenging. Herein, cells that play a key role in bone healing will be reviewed and extracellular mediators regulating their behavior discussed. We will focus on recent studies that explore novel roles of inflammation in bone healing, and the origins and fates of various cells in the fracture environment. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res Advances in transgenic and gene‐targeted mice have enabled tissue and cell‐specific investigation of skeletal regeneration. While genetically modified animals offer incredible insights into the temporal and spatial importance of various molecules, the complexity and rapidity of healing renders studies of regenerative biology challenging. Herein, cells and extracellular mediators that play a key role in bone healing are reviewed. We will focus on recent studies that explore the origins and fates of various cells in the fracture environment. [ABSTRACT FROM AUTHOR]

ABSTRACT: Geriatric fractures take longer to heal and heal with more complications than those of younger patients; however, the mechanistic basis for this difference in healing is not well understood. To improve this understanding, we investigated cell and molecular differences in fracture healing between 5‐month‐old (young adult) and 25‐month‐old (geriatric) mice healing utilizing high‐throughput analysis of gene expression. Mice underwent bilateral tibial fractures and fracture calluses were harvested at 5, 10, and 20 days post‐fracture (DPF) for analysis. Global gene expression analysis was performed using Affymetrix MoGene 1.0 ST microarrays. After normalization, data were compared using ANOVA and evaluated using Principal Component Analysis (PCA), CTen, heatmap, and Incromaps analysis. PCA and cross‐sectional heatmap analysis demonstrated that DPF followed by age had pronounced effects on changes in gene expression. Both un‐fractured and 20 DPF aged mice showed increased expression of immune‐associated genes (CXCL8, CCL8, and CCL5) and at 10 DPF, aged mice showed increased expression of matrix‐associated genes, (Matn1, Ucma, Scube1, Col9a1, and Col9a3). Cten analysis suggested an enrichment of CD8+ cells and macrophages in old mice relative to young adult mice and, conversely, a greater prevalence of mast cells in young adult mice relative to old. Finally, consistent with the PCA data, the classic bone healing pathways of BMP, Indian Hedgehog, Notch and Wnt clustered according to the time post‐fracture first and age second. Clinical Significance: Greater understanding of age‐dependent molecular changes with healing will help form a mechanistic basis for therapies to improve patient outcomes. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:149–158, 2018. [ABSTRACT FROM AUTHOR]