Browsing by Subject "fracture healing"

Now showing 1 - 3 of 3
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    Characterization and assessment of lung and bone marrow derived endothelial cells and their bone regenerative potential
    (Frontiers, 2022) de Lima Perini, Mariana Moraes; Valuch, Conner R.; Dadwal, Ushashi C.; Awosanya, Olatundun D.; Mostardo, Sarah L.; Blosser, Rachel J.; Knox, Adam M.; McGuire, Anthony C.; Battina, Hanisha L.; Nazzal, Murad; Kacena, Melissa A.; Li, Jiliang; Biology, School of Science
    Angiogenesis is important for successful fracture repair. Aging negatively affects the number and activity of endothelial cells (ECs) and subsequently leads to impaired bone healing. We previously showed that implantation of lung-derived endothelial cells (LECs) improved fracture healing in rats. In this study, we characterized and compared neonatal lung and bone marrow-derived endothelial cells (neonatal LECs and neonatal BMECs) and further asses3sed if implantation of neonatal BMECs could enhance bone healing in both young and aged mice. We assessed neonatal EC tube formation, proliferation, and wound migration ability in vitro in ECs isolated from the bone marrow and lungs of neonatal mice. The in vitro studies demonstrated that both neonatal LECs and neonatal BMECs exhibited EC traits. To test the function of neonatal ECs in vivo, we created a femoral fracture in young and aged mice and implanted a collagen sponge to deliver neonatal BMECs at the fracture site. In the mouse fracture model, endochondral ossification was delayed in aged control mice compared to young controls. Neonatal BMECs significantly improved endochondral bone formation only in aged mice. These data suggest BMECs have potential to enhance aged bone healing. Compared to LECs, BMECs are more feasible for translational cell therapy and clinical applications in bone repair. Future studies are needed to examine the fate and function of BMECs implanted into the fracture sites.
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    Inhibition of CaMKK2 Enhances Fracture Healing by Stimulating Indian Hedgehog Signaling and Accelerating Endochondral Ossification
    (Wiley, 2018) Williams, Justin N.; Kambrath, Anuradha Valiya; Patel, Roshni B.; Kang, Kyung Shin; Mével, Elsa; Li, Yong; Cheng, Ying-Hua; Pucylowski, Austin J.; Hassert, Mariah A.; Voor, Michael J.; Kacena, Melissa A.; Thompson, William R.; Warden, Stuart J.; Burr, David B.; Allen, Matthew R.; Robling, Alexander G.; Sankar, Uma; Anatomy and Cell Biology, School of Medicine
    Approximately 10% of all bone fractures do not heal, resulting in patient morbidity and healthcare costs. However, no pharmacological treatments are currently available to promote efficient bone healing. Inhibition of Ca2+/calmodulin (CaM)-dependent protein kinase kinase 2 (CaMKK2) reverses age-associated loss of trabecular and cortical bone volume and strength in mice. In the current study, we investigated the role of CaMKK2 in bone fracture healing and show that its pharmacological inhibition using STO-609 accelerates early cellular and molecular events associated with endochondral ossification, resulting in a more rapid and efficient healing of the fracture. Within 7 days postfracture, treatment with STO-609 resulted in enhanced Indian hedgehog signaling, paired-related homeobox (PRX1)-positive mesenchymal stem cell (MSC) recruitment, and chondrocyte differentiation and hypertrophy, along with elevated expression of osterix, vascular endothelial growth factor, and type 1 collagen at the fracture callus. Early deposition of primary bone by osteoblasts resulted in STO-609–treated mice possessing significantly higher callus bone volume by 14 days following fracture. Subsequent rapid maturation of the bone matrix bestowed fractured bones in STO-609–treated animals with significantly higher torsional strength and stiffness by 28 days postinjury, indicating accelerated healing of the fracture. Previous studies indicate that fixed and closed femoral fractures in the mice take 35 days to fully heal without treatment. Therefore, our data suggest that STO-609 potentiates a 20% acceleration of the bone healing process. Moreover, inhibiting CaMKK2 also imparted higher mechanical strength and stiffness at the contralateral cortical bone within 4 weeks of treatment. Taken together, the data presented here underscore the therapeutic potential of targeting CaMKK2 to promote efficacious and rapid healing of bone fractures and as a mechanism to strengthen normal bones.
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    Methodology, selection, and integration of fracture healing assessments in mice
    (Wiley, 2021-11) Knox, Adam M.; McGuire, Anthony C.; Natoli, Roman M.; Kacena, Melissa A.; Collier, Christopher D.; Orthopaedic Surgery, School of Medicine
    Long bone fractures are one of the most common and costly medical conditions encountered after trauma. Characterization of the biology of fracture healing and development of potential medical interventions generally involves animal models of fracture healing using varying genetic or treatment groups, then analyzing relative repair success via the synthesis of diverse assessment methodologies. Murine models are some of the most widely used given their low cost, wide variety of genetic variants, and rapid breeding and maturation. This review addresses key concerns regarding fracture repair investigations in mice and may serve as a guide in conducting and interpreting such studies. Specifically, this review details the procedures, highlights relevant parameters, and discusses special considerations for the selection and integration of the major modalities used for quantifying fracture repair in such studies, including X-ray, microcomputed tomography, histomorphometric, biomechanical, gene expression and biomarker analyses.