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  • Brommage, RobertGothenburg 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 (author)

NOTUM inhibition increases endocortical bone formation and bone strength

  • Article/chapterEnglish2019

Publisher, publication year, extent ...

  • 2019-01-08
  • Springer Science and Business Media LLC,2019

Numbers

  • LIBRIS-ID:oai:gup.ub.gu.se/276837
  • https://gup.ub.gu.se/publication/276837URI
  • https://doi.org/10.1038/s41413-018-0038-3DOI

Supplementary language notes

  • Language:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • The disability, mortality and costs caused by non-vertebral osteoporotic fractures are enormous. Existing osteoporosis therapies are highly effective at reducing vertebral but not non-vertebral fractures. Cortical bone is a major determinant of non-vertebral bone strength. To identify novel osteoporosis drug targets, we phenotyped cortical bone of 3 366 viable mouse strains with global knockouts of druggable genes. Cortical bone thickness was substantially elevated in Notum(-/-) mice. NOTUM is a secreted WNT lipase and we observed high NOTUM expression in cortical bone and osteoblasts but not osteoclasts. Three orally active small molecules and a neutralizing antibody inhibiting NOTUM lipase activity were developed. They increased cortical bone thickness and strength at multiple skeletal sites in both gonadal intact and ovariectomized rodents by stimulating endocortical bone formation. Thus, inhibition of NOTUM activity is a potential novel anabolic therapy for strengthening cortical bone and preventing non-vertebral fractures.

Subject headings and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • Liu, J. (author)
  • Vogel, P. (author)
  • Mseeh, F. (author)
  • Thompson, A. Y. (author)
  • Potter, D. G. (author)
  • Shadoan, M. K. (author)
  • Hansen, G. M. (author)
  • Jeter-Jones, S. (author)
  • Cui, J. (author)
  • Bright, D. (author)
  • Bardenhagen, J. P. (author)
  • Doree, D. D. (author)
  • Moverare-Skrtic, SofiaGothenburg 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(Swepub:gu)xmovso (author)
  • Nilsson, Karin H.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(Swepub:gu)xnkarl (author)
  • Henning, Petra,1974Gothenburg 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(Swepub:gu)xhenpe (author)
  • Lerner, Ulf HGothenburg 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(Swepub:gu)xlerul (author)
  • Ohlsson, Claes,1965Gothenburg 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(Swepub:gu)xohlcl (author)
  • Sands, A. T. (author)
  • Tarver, J. E. (author)
  • Powell, D. R. (author)
  • Zambrowicz, B. (author)
  • Liu, Q. Y. (author)
  • Göteborgs universitetInstitutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition (creator_code:org_t)

Related titles

  • In:Bone Research: Springer Science and Business Media LLC7:22095-47002095-6231

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