WNT16 is Robustly Increased by Oncostatin M in Mouse Calvarial Osteoblasts and Acts as a Negative Feedback Regulator of Osteoclast Formation Induced by Oncostatin M
Petra Henning,1 Sofia Movérare-Skrtic,1 Anna Westerlund,1 Pedro Paulo Chaves de Souza,2,3 Thais Floriano-Marcelino,3 Karin H Nilsson,1 Maha El Shahawy,1,4 Claes Ohlsson,1 Ulf H Lerner1 1Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Osteoporosis Centre and...
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Dove Medical Press
2021
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oai:doaj.org-article:38926c83b408444a962d180638aa93592021-12-02T18:02:09ZWNT16 is Robustly Increased by Oncostatin M in Mouse Calvarial Osteoblasts and Acts as a Negative Feedback Regulator of Osteoclast Formation Induced by Oncostatin M1178-7031https://doaj.org/article/38926c83b408444a962d180638aa93592021-09-01T00:00:00Zhttps://www.dovepress.com/wnt16-is-robustly-increased-by-oncostatin-m-in-mouse-calvarial-osteobl-peer-reviewed-fulltext-article-JIRhttps://doaj.org/toc/1178-7031Petra Henning,1 Sofia Movérare-Skrtic,1 Anna Westerlund,1 Pedro Paulo Chaves de Souza,2,3 Thais Floriano-Marcelino,3 Karin H Nilsson,1 Maha El Shahawy,1,4 Claes Ohlsson,1 Ulf H Lerner1 1Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Osteoporosis Centre and Centre for Bone and Arthritis Research at the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; 2The Innovation in Biomaterials Laboratory, School of Dentistry, Federal University of Goiás, Goiânia, Brazil; 3Department of Physiology and Pathology, São Paulo State University (UNESP), School of Dentistry, Araraquara, Brazil; 4Department of Oral Biology, Faculty of Dentistry, Minia University, Minia, 61511, EgyptCorrespondence: Ulf H LernerUniversity of Gothenburg, Klin Farm Lab, Vita Straket 11, Gothenburg, 41345, SwedenTel +46 70 651 91 03Email ulf.lerner@gu.seBackground: Bone loss is often observed adjacent to inflammatory processes. The WNT signaling pathways have been implicated as novel regulators of both immune responses and bone metabolism. WNT16 is important for cortical bone mass by inhibiting osteoclast differentiation, and we have here investigated the regulation of WNT16 by several members of the pro-inflammatory gp130 cytokine family.Methods: The expression and regulation of Wnt16 in primary murine cells were studied by qPCR, scRNAseq and in situ hybridization. Signaling pathways were studied by siRNA silencing. The importance of oncostatin M (OSM)-induced WNT16 expression for osteoclastogenesis was studied in cells from Wnt16-deficient and wild-type mice.Results: We found that IL-6/sIL-6R and OSM induce the expression of Wnt16 in primary mouse calvarial osteoblasts, with OSM being the most robust stimulator. The induction of Wnt16 by OSM was dependent on gp130 and OSM receptor (OSMR), and downstream signaling by the SHC1/STAT3 pathway, but independent of ERK. Stimulation of the calvarial cells with OSM resulted in enhanced numbers of mature, oversized osteoclasts when cells were isolated from Wnt16 deficient mice compared to cells from wild-type mice. OSM did not affect Wnt16 mRNA expression in bone marrow cell cultures, explained by the finding that Wnt16 and Osmr are expressed in distinctly different cells in bone marrow, nor was osteoclast differentiation different in OSM-stimulated bone marrow cell cultures isolated from Wnt16−/- or wild-type mice. Furthermore, we found that Wnt16 expression is substantially lower in cells from bone marrow compared to calvarial osteoblasts.Conclusion: These findings demonstrate that OSM is a robust stimulator of Wnt16 mRNA in calvarial osteoblasts and that WNT16 acts as a negative feedback regulator of OSM-induced osteoclast formation in the calvarial bone cells, but not in the bone marrow.Keywords: oncostatin M, WNT16, osteoclast, osteoblastHenning PMovérare-Skrtic SWesterlund ASouza PPCFloriano-Marcelino TNilsson KHEl Shahawy MOhlsson CLerner UHDove Medical Pressarticleoncostatin mwnt16osteoclastosteoblastPathologyRB1-214Therapeutics. PharmacologyRM1-950ENJournal of Inflammation Research, Vol Volume 14, Pp 4723-4741 (2021) |
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DOAJ |
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EN |
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oncostatin m wnt16 osteoclast osteoblast Pathology RB1-214 Therapeutics. Pharmacology RM1-950 |
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oncostatin m wnt16 osteoclast osteoblast Pathology RB1-214 Therapeutics. Pharmacology RM1-950 Henning P Movérare-Skrtic S Westerlund A Souza PPC Floriano-Marcelino T Nilsson KH El Shahawy M Ohlsson C Lerner UH WNT16 is Robustly Increased by Oncostatin M in Mouse Calvarial Osteoblasts and Acts as a Negative Feedback Regulator of Osteoclast Formation Induced by Oncostatin M |
| description |
Petra Henning,1 Sofia Movérare-Skrtic,1 Anna Westerlund,1 Pedro Paulo Chaves de Souza,2,3 Thais Floriano-Marcelino,3 Karin H Nilsson,1 Maha El Shahawy,1,4 Claes Ohlsson,1 Ulf H Lerner1 1Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Osteoporosis Centre and Centre for Bone and Arthritis Research at the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; 2The Innovation in Biomaterials Laboratory, School of Dentistry, Federal University of Goiás, Goiânia, Brazil; 3Department of Physiology and Pathology, São Paulo State University (UNESP), School of Dentistry, Araraquara, Brazil; 4Department of Oral Biology, Faculty of Dentistry, Minia University, Minia, 61511, EgyptCorrespondence: Ulf H LernerUniversity of Gothenburg, Klin Farm Lab, Vita Straket 11, Gothenburg, 41345, SwedenTel +46 70 651 91 03Email ulf.lerner@gu.seBackground: Bone loss is often observed adjacent to inflammatory processes. The WNT signaling pathways have been implicated as novel regulators of both immune responses and bone metabolism. WNT16 is important for cortical bone mass by inhibiting osteoclast differentiation, and we have here investigated the regulation of WNT16 by several members of the pro-inflammatory gp130 cytokine family.Methods: The expression and regulation of Wnt16 in primary murine cells were studied by qPCR, scRNAseq and in situ hybridization. Signaling pathways were studied by siRNA silencing. The importance of oncostatin M (OSM)-induced WNT16 expression for osteoclastogenesis was studied in cells from Wnt16-deficient and wild-type mice.Results: We found that IL-6/sIL-6R and OSM induce the expression of Wnt16 in primary mouse calvarial osteoblasts, with OSM being the most robust stimulator. The induction of Wnt16 by OSM was dependent on gp130 and OSM receptor (OSMR), and downstream signaling by the SHC1/STAT3 pathway, but independent of ERK. Stimulation of the calvarial cells with OSM resulted in enhanced numbers of mature, oversized osteoclasts when cells were isolated from Wnt16 deficient mice compared to cells from wild-type mice. OSM did not affect Wnt16 mRNA expression in bone marrow cell cultures, explained by the finding that Wnt16 and Osmr are expressed in distinctly different cells in bone marrow, nor was osteoclast differentiation different in OSM-stimulated bone marrow cell cultures isolated from Wnt16−/- or wild-type mice. Furthermore, we found that Wnt16 expression is substantially lower in cells from bone marrow compared to calvarial osteoblasts.Conclusion: These findings demonstrate that OSM is a robust stimulator of Wnt16 mRNA in calvarial osteoblasts and that WNT16 acts as a negative feedback regulator of OSM-induced osteoclast formation in the calvarial bone cells, but not in the bone marrow.Keywords: oncostatin M, WNT16, osteoclast, osteoblast |
| format |
article |
| author |
Henning P Movérare-Skrtic S Westerlund A Souza PPC Floriano-Marcelino T Nilsson KH El Shahawy M Ohlsson C Lerner UH |
| author_facet |
Henning P Movérare-Skrtic S Westerlund A Souza PPC Floriano-Marcelino T Nilsson KH El Shahawy M Ohlsson C Lerner UH |
| author_sort |
Henning P |
| title |
WNT16 is Robustly Increased by Oncostatin M in Mouse Calvarial Osteoblasts and Acts as a Negative Feedback Regulator of Osteoclast Formation Induced by Oncostatin M |
| title_short |
WNT16 is Robustly Increased by Oncostatin M in Mouse Calvarial Osteoblasts and Acts as a Negative Feedback Regulator of Osteoclast Formation Induced by Oncostatin M |
| title_full |
WNT16 is Robustly Increased by Oncostatin M in Mouse Calvarial Osteoblasts and Acts as a Negative Feedback Regulator of Osteoclast Formation Induced by Oncostatin M |
| title_fullStr |
WNT16 is Robustly Increased by Oncostatin M in Mouse Calvarial Osteoblasts and Acts as a Negative Feedback Regulator of Osteoclast Formation Induced by Oncostatin M |
| title_full_unstemmed |
WNT16 is Robustly Increased by Oncostatin M in Mouse Calvarial Osteoblasts and Acts as a Negative Feedback Regulator of Osteoclast Formation Induced by Oncostatin M |
| title_sort |
wnt16 is robustly increased by oncostatin m in mouse calvarial osteoblasts and acts as a negative feedback regulator of osteoclast formation induced by oncostatin m |
| publisher |
Dove Medical Press |
| publishDate |
2021 |
| url |
https://doaj.org/article/38926c83b408444a962d180638aa9359 |
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