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Sökning: WFRF:(Movérare Skrtic Sofia) > (2020-2024) > The novel cytotoxic...

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

Henning, Petra, 1974 (författare)
Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition,Centre for Bone and Arthritis Research,Institute of Medicine, Department of Internal Medicine and Clinical Nutrition,Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Osteoporosis Centre, Sahlgrenska Academy at the University of Gothenburg, Vita Stråket 11, Gothenburg, Sweden
Westerlund, Anna, 1981 (författare)
Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition,Centre for Bone and Arthritis Research,Institute of Medicine, Department of Internal Medicine and Clinical Nutrition,Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Osteoporosis Centre, Sahlgrenska Academy at the University of Gothenburg, Vita Stråket 11, Gothenburg, Sweden
Moverare-Skrtic, Sofia (författare)
Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition,Centre for Bone and Arthritis Research,Institute of Medicine, Department of Internal Medicine and Clinical Nutrition,Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Osteoporosis Centre, Sahlgrenska Academy at the University of Gothenburg, Vita Stråket 11, Gothenburg, Sweden
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Lindholm, Catharina, 1967 (författare)
Gothenburg University,Göteborgs universitet,Centre for Bone and Arthritis Research,Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Osteoporosis Centre, Sahlgrenska Academy at the University of Gothenburg, Vita Stråket 11, Gothenburg, Sweden
Marquez-Mendez, Marcela (författare)
Karolinska Institutet,Department of Oncology and Pathology, Karolinska Institute, Stockholm, Sweden
Nilsson, Sten (författare)
Department of Oncology and Pathology, Karolinska Institute, Stockholm, Sweden
Holmberg, Anders R. (författare)
Department of Oncology and Pathology, Karolinska Institute, Stockholm, Sweden
Lerner, Ulf H (författare)
Umeå universitet,Gothenburg University,Göteborgs universitet,Centre for Bone and Arthritis Research,Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition,Institute of Medicine, Department of Internal Medicine and Clinical Nutrition,Institutionen för odontologi,Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Osteoporosis Centre, Sahlgrenska Academy at the University of Gothenburg, Vita Stråket 11, Gothenburg, Sweden
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 (creator_code:org_t)
Springer, 2024
2024
Engelska.
Ingår i: INVESTIGATIONAL NEW DRUGS. - : Springer. - 0167-6997 .- 1573-0646.
Relaterad länk:
https://doi.org/10.1...
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https://umu.diva-por... (primary) (Raw object)
https://gup.ub.gu.se...
https://doi.org/10.1...
http://kipublication...
https://urn.kb.se/re...
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  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
Stäng  
  • 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)

Nyckelord

Bisphosphonates
Osteodex
Osteoclasts
RANKL
Bisphosphonates

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