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- de Souza, P. P. C. (författare)
Stimulation of Osteoclast Formation by Oncostatin M and the Role of WNT16 as a Negative Feedback Regulator
- Artikel/kapitelEngelska2022
Förlag, utgivningsår, omfång ...
- 2022-03-18
- MDPI AG,2022
Nummerbeteckningar
- LIBRIS-ID:oai:gup.ub.gu.se/315271
- https://gup.ub.gu.se/publication/315271URI
- https://doi.org/10.3390/ijms23063287DOI
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- Språk:engelska
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- Oncostatin M (OSM), which belongs to the IL-6 family of cytokines, is the most potent and effective stimulator of osteoclast formation in this family, as assessed by different in vitro assays. Osteoclastogenesis induced by the IL-6 type of cytokines is mediated by the induction and paracrine stimulation of the osteoclastogenic cytokine receptor activator of nuclear factor kappa-B ligand (RANKL), expressed on osteoblast cell membranes and targeting the receptor activator of nuclear factor kappa-B (RANK) on osteoclast progenitor cells. The potent effect of OSM on osteoclastogenesis is due to an unusually robust induction of RANKL in osteoblasts through the OSM receptor (OSMR), mediated by a JAK-STAT/MAPK signaling pathway and by unique recruitment of the adapter protein Shc1 to the OSMR. Gene deletion of Osmr in mice results in decreased numbers of osteoclasts and enhanced trabecular bone caused by increased trabecular thickness, indicating that OSM may play a role in physiological regulation of bone remodeling. However, increased amounts of OSM, either through administration of recombinant protein or of adenoviral vectors expressing Osm, results in enhanced bone mass due to increased bone formation without any clear sign of increased osteoclast numbers, a finding which can be reconciled by cell culture experiments demonstrating that OSM can induce osteoblast differentiation and stimulate mineralization of bone nodules in such cultures. Thus, in vitro studies and gene deletion experiments show that OSM is a stimulator of osteoclast formation, whereas administration of OSM to mice shows that OSM is not a strong stimulator of osteoclastogenesis in vivo when administered to adult animals. These observations could be explained by our recent finding showing that OSM is a potent stimulator of the osteoclastogenesis inhibitor WNT16, acting in a negative feedback loop to reduce OSM-induced osteoclast formation.
Ämnesord och genrebeteckningar
- NATURVETENSKAP Biologi Biokemi och molekylärbiologi hsv//swe
- NATURAL SCIENCES Biological Sciences Biochemistry and Molecular Biology hsv//eng
- OSM
- WNT16
- RANKL
- osteoclast
- bone resorption
- leukemia-inhibitory factor
- kappa-b ligand
- signal transducer gp130
- phase response factor/stat3
- ciliary neurotrophic factor
- jak-tyk
- kinases
- receptor-activator
- bone-formation
- crystal-structure
- nuclear-factor
- Biochemistry & Molecular Biology
- Chemistry
Biuppslag (personer, institutioner, konferenser, titlar ...)
- Henning, Petra,1974Gothenburg 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)xhenpe (författare)
- 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 (författare)
- Göteborgs universitetCentre for Bone and Arthritis Research (creator_code:org_t)
Sammanhörande titlar
- Ingår i:International Journal of Molecular Sciences: MDPI AG23:61422-0067
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