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Unlabelled: CP432 is a newly discovered, nonprostanoid EP4 receptor selective prostaglandin E2 agonist. CP432 stimulates trabecular and cortical bone formation and restores bone mass and bone strength in aged ovariectomized rats with established osteopenia.
Introduction: The purpose of this study was to determine whether a newly discovered, nonprostanoid EP4 receptor selective prostaglandin E2 (PGE2) agonist, CP432, could produce bone anabolic effects in aged, ovariectomized (OVX) rats with established osteopenia.
Materials And Methods: CP432 at 0.3, 1, or 3 mg/kg/day was given for 6 weeks by subcutaneous injection to 12-month-old rats that had been OVX for 8.5 months. The effects on bone mass, bone formation, bone resorption, and bone strength were determined.
Results: Total femoral BMD increased significantly in OVX rats treated with CP432 at all doses. CP432 completely restored trabecular bone volume of the third lumbar vertebral body accompanied with a dose-dependent decrease in osteoclast number and osteoclast surface and a dose-dependent increase in mineralizing surface, mineral apposition rate, and bone formation rate-tissue reference in OVX rats. CP432 at 1 and 3 mg/kg/day significantly increased total tissue area, cortical bone area, and periosteal and endocortical bone formation in the tibial shafts compared with both sham and OVX controls. CP432 at all doses significantly and dose-dependently increased ultimate strength in the fifth lumber vertebral body compared with both sham and OVX controls. At 1 and 3 mg/kg/day, CP432 significantly increased maximal load in a three-point bending test of femoral shaft compared with both sham and OVX controls.
Conclusions: CP432 completely restored trabecular and cortical bone mass and strength in established osteopenic, aged OVX rats by stimulating bone formation and inhibiting bone resorption on trabecular and cortical surfaces.
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http://dx.doi.org/10.1359/jbmr.051110 | DOI Listing |
Cell Mol Life Sci
December 2024
Center for Mitochondrial Research and Medicine, College of Medicine Chang Gung University, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
Imbalances in gut microbiota and their metabolites have been implicated in osteoporotic disorders. Trimethylamine-n-oxide (TMAO), a metabolite of L-carnitine produced by gut microorganisms and flavin-containing monooxygenase-3, is known to accelerate tissue metabolism and remodeling; however, its role in bone loss remained unexplored. This study investigates the relationship between gut microbiota dysbiosis, TMAO production, and osteoporosis development.
View Article and Find Full Text PDFACS Appl Mater Interfaces
December 2024
Molecular Oncology Laboratory, Department of Orthopedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center; Chicago, Illinois 60637, United States.
Effective repair of large bone defects through bone tissue engineering (BTE) remains an unmet clinical challenge. Successful BTE requires optimal and synergistic interactions among biocompatible scaffolds, osteogenic factors, and osteoprogenitors to form a highly vascularized microenvironment for bone regeneration and osseointegration. We sought to develop a highly effective BTE system by using 3D printed citrate-based mPOC/hydroxyapatite (HA) composites laden with BMP9-stimulated human urine stem cells (USCs).
View Article and Find Full Text PDFTissue Eng Part A
December 2024
Department of Orthopedics, Municipal Hospital Affiliated to Taizhou University, Taizhou City, China.
Senescence and osteogenic differentiation potential loss limited bone nonunion treatment effects of bone marrow-derived mesenchymal stem cells (BMSCs). MiR-100-5p/Lysine(K)-specific demethylase 6B (KDM6B) can inhibit osteogenesis, but their effects on bone union remain unclear. This study aims to investigate the effects of miR-100-5p/KDM6B on osteogenic differentiation and bone defects.
View Article and Find Full Text PDFHum Cell
December 2024
Department of Integrative Bioscience and Biotechnology, Institute of Bioscience, Institute of Anticancer Medicine Development, Sejong University, Seoul, 143-747, Korea.
Human pluripotent stem cells (hPSCs) have at least three distinct states: naïve pluripotency that represents the cellular states of the pre-implantation epiblast cells, primed pluripotency that represents the cellular states of the post-implantation epiblast cells, and formative pluripotency that represents a developmental continuum between naïve and primed pluripotency. Various cell surface markers have been used to define and analyze primed and naïve hPSCs within heterogeneous populations. However, not much is known about common cell surface markers for the different pluripotent states of hPSCs.
View Article and Find Full Text PDFEur J Orthop Surg Traumatol
December 2024
Saint Paul hospital Millenium Medical College, Addis Ababa, Ethiopia.
Background: Due to the specific anatomical features of the tibia (limited soft tissue coverage), more than a quarter of its fractures are classified as open, representing the most common open long-bone injuries. Open tibial fractures frequently cause significant bone comminution, periosteal stripping, soft tissue loss, contamination and are prone to bacterial entry with biofilm formation, which increases the risk of deep bone infection. The main objective of this study was to determine prevalence of infection and its associated factors in surgically treated open tibial fracture, at Addis Ababa Burn Emergency and Trauma (AaBET) hospital.
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