학술논문
The novel cytotoxic polybisphosphonate osteodex decreases bone resorption by enhancing cell death of mature osteoclasts without affecting osteoclastogenesis of RANKL-stimulated mouse bone marrow macrophages.
Document Type
Academic Journal
Author
Henning P; Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Osteoporosis Centre, Sahlgrenska Academy at the University of Gothenburg, Vita Stråket 11, Gothenburg 41345, Sweden.; Westerlund A; Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Osteoporosis Centre, Sahlgrenska Academy at the University of Gothenburg, Vita Stråket 11, Gothenburg 41345, Sweden.; Movérare-Skrtic S; Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Osteoporosis Centre, Sahlgrenska Academy at the University of Gothenburg, Vita Stråket 11, Gothenburg 41345, Sweden.; Lindholm C; Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Osteoporosis Centre, Sahlgrenska Academy at the University of Gothenburg, Vita Stråket 11, Gothenburg 41345, Sweden.; Márquez-Méndez M; Department of Oncology and Pathology, Karolinska Institute, Stockholm SE-171 76, Sweden.; Nilsson S; Department of Oncology and Pathology, Karolinska Institute, Stockholm SE-171 76, Sweden.; Holmberg AR; Department of Oncology and Pathology, Karolinska Institute, Stockholm SE-171 76, Sweden.; Lerner UH; Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Osteoporosis Centre, Sahlgrenska Academy at the University of Gothenburg, Vita Stråket 11, Gothenburg 41345, Sweden. ulf.lerner@gu.se.; Molecular Periodontology, Faculty of Medicine, Umeå University, SE-901 87, Umeå, Sweden. ulf.lerner@gu.se.
Source
Publisher: Springer Country of Publication: United States NLM ID: 8309330 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1573-0646 (Electronic) Linking ISSN: 01676997 NLM ISO Abbreviation: Invest New Drugs Subsets: MEDLINE
Subject
Language
English
Abstract
It has previously been demonstrated that the polybisphosphonate osteodex (ODX) inhibits bone resorption in organ-cultured mouse calvarial bone. In this study, we further investigate the effects by ODX on osteoclast differentiation, formation, and function in several different bone organ and cell cultures. Zoledronic acid (ZOL) was used for comparison. In retinoid-stimulated mouse calvarial organ cultures, ODX and ZOL significantly reduced the numbers of periosteal osteoclasts without affecting Tnfsf11 or Tnfrsf11b mRNA expression. ODX and ZOL also drastically reduced the numbers of osteoclasts in cell cultures isolated from the calvarial bone and in vitamin D3-stimulated mouse crude bone marrow cell cultures. These data suggest that ODX can inhibit osteoclast formation by inhibiting the differentiation of osteoclast progenitor cells or by directly targeting mature osteoclasts. We therefore assessed if osteoclast formation in purified bone marrow macrophage cultures stimulated by RANKL was inhibited by ODX and ZOL and found that the initial formation of mature osteoclasts was not affected, but that the bisphosphonates enhanced cell death of mature osteoclasts. In agreement with these findings, ODX and ZOL did not affect the mRNA expression of the osteoclastic genes Acp5 and Ctsk and the osteoclastogenic transcription factor Nfatc1. When bone marrow macrophages were incubated on bone slices, ODX and ZOL inhibited RANKL-stimulated bone resorption. In conclusion, ODX does not inhibit osteoclast formation but inhibits osteoclastic bone resorption by decreasing osteoclast numbers through enhanced cell death of mature osteoclasts.
(© 2024. The Author(s).)
(© 2024. The Author(s).)