Cyclosporine a inhibits bone regeneration and induces bone loss in a rat model.

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  • Author(s): Tao ZS;Tao ZS;Tao ZS; Ma T; Ma T; Yang M; Yang M
  • Source:
    International immunopharmacology [Int Immunopharmacol] 2024 May 10; Vol. 132, pp. 111951. Date of Electronic Publication: 2024 Mar 29.
  • Publication Type:
    Journal Article
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: Elsevier Science Country of Publication: Netherlands NLM ID: 100965259 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1878-1705 (Electronic) Linking ISSN: 15675769 NLM ISO Abbreviation: Int Immunopharmacol Subsets: MEDLINE
    • Publication Information:
      Original Publication: Amsterdam ; New York : Elsevier Science, c2001-
    • Subject Terms:
      Bone Regeneration*/drug effects ; Cyclosporine*/pharmacology ; Osteogenesis*/drug effects ; Ovariectomy* ; Rats, Sprague-Dawley* ; Osteoblasts*/drug effects ; Cell Differentiation*/drug effects ; Disease Models, Animal*; Animals ; Female ; Mice ; Rats ; Cell Line ; Osteoporosis/drug therapy ; Humans ; Femur/drug effects ; Femur/diagnostic imaging ; Femur/pathology ; Immunosuppressive Agents/pharmacology ; Immunosuppressive Agents/therapeutic use ; Osteoporosis, Postmenopausal/drug therapy
    • Abstract:
      Cyclosporine A (CSA) is an immunosuppressant that has been extensively studied for its side effects on inhibiting osseointegration of titanium implants. However, the impact of CSA on bone healing in postmenopausal osteoporosis remains unknown. Therefore, this study aimed to investigate the effect of CSA on bone repair in an ovariectomized (OVX) rat model through both in vitro and in vivo experiments. We examined the interventions of CSA on osteoblast progenitor cells MC3T3-E1 and assessed their effects on biological function using RT-qPCR, CCK-8 assay, alizarin red staining, and alkaline phosphatase staining. Furthermore, we evaluated the effects of CSA on bone regeneration and bone mass in both OVX rat models and femoral diaphysis bone defect models. The results from the CCK-8 experiment indicated a positive influence of experimental doses of CSA on osteogenic differentiation of MC3T3-E1 cells. ALP expression levels and calcified nodules were also evaluated, suggesting that CSA intervention promoted osteogenic differentiation in MC3T3-E1 cells. Additionally, specific gene expressions including OPN, Runx-2, OC, and Col1a1 were up-regulated after CSA intervention. Biomechanical parameters aligned with histological analysis as well as micro-CT scans confirmed worse bone microstructure and strength following CSA intervention. Our findings preliminarily suggest that whether it is normal or osteoporotic bones, CSA has adverse effects on bone health which are associated with elevated-bone turnover.
      Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
      (Copyright © 2024 Elsevier B.V. All rights reserved.)
    • Contributed Indexing:
      Keywords: Bone mass; Bone regeneration; Bone turnover; Cyclosporine A; Osteoporosis
    • Accession Number:
      83HN0GTJ6D (Cyclosporine)
      0 (Immunosuppressive Agents)
    • Publication Date:
      Date Created: 20240329 Date Completed: 20240430 Latest Revision: 20240430
    • Publication Date:
      20240430
    • Accession Number:
      10.1016/j.intimp.2024.111951
    • Accession Number:
      38552293