{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T01:10:20Z","timestamp":1784855420721,"version":"3.55.0"},"reference-count":53,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2022,6,8]],"date-time":"2022-06-08T00:00:00Z","timestamp":1654646400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Deutsche Forschungsgemeinschaft"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Chronic kidney disease (CKD) frequently leads to hyperphosphatemia and hyperparathyroidism, mineral bone disorder (CKD-MBD), ectopic calcifications and cardiovascular mortality. PTH activates the osteoanabolic G\u03b1s\/PKA and the G\u03b1q\/11\/PKC pathways in osteoblasts, the specific impact of the latter in CKD-MBD is unknown. We generated osteoblast specific G\u03b1q\/11 knockout (KO) mice and established CKD-MBD by subtotal nephrectomy and dietary phosphate load. Bone morphology was assessed by micro-CT, osteoblast function by bone planar scintigraphy at week 10 and 22 and by histomorphometry. Osteoblasts isolated from G\u03b1q\/11 KO mice increased cAMP but not IP3 in response to PTH 1-34, demonstrating the specific KO of the PKC signaling pathway. Osteoblast specific G\u03b1q\/11 KO mice exhibited increased serum calcium and reduced bone cortical thickness and mineral density at 24 weeks. CKD G\u03b1q\/11 KO mice had similar bone morphology compared to WT, while CKD G\u03b1q\/11-KO on high phosphate diet developed decreased metaphyseal and diaphyseal cortical thickness and area, as well as a reduction in trabecular number. G\u03b1q\/11-KO increased bone scintigraphic tracer uptake at week 10 and mitigated tracer uptake in CKD mice at week 22. Histological bone parameters indicated similar trends. G\u03b1q\/11-KO in osteoblast modulates calcium homeostasis, bone formation rate, bone morphometry, and bone mineral density. In CKD and high dietary phosphate intake, osteoblast G\u03b1q\/11\/PKC KO further aggravates mineral bone disease.<\/jats:p>","DOI":"10.3390\/ijms23126404","type":"journal-article","created":{"date-parts":[[2022,6,10]],"date-time":"2022-06-10T02:25:33Z","timestamp":1654827933000},"page":"6404","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Inactivation of Osteoblast PKC Signaling Reduces Cortical Bone Mass and Density and Aggravates Renal Osteodystrophy in Mice with Chronic Kidney Disease on High Phosphate Diet"],"prefix":"10.3390","volume":"23","author":[{"given":"Ariane","family":"Zaloszyc","sequence":"first","affiliation":[{"name":"Service de P\u00e9diatrie 1, H\u00f4pital de Hautepierre, H\u00f4pitaux Universitaires de Strasbourg, 67098 Strasbourg, France"},{"name":"Imagerie Pr\u00e9clinique\u2014UF6237, P\u00f4le d\u2019Imagerie, H\u00f4pitaux Universitaires de Strasbourg, 67098 Strasbourg, France"},{"name":"OMICARE, Centre de Recherche d\u2019Immunologie et d\u2019H\u00e9matologie, F\u00e9d\u00e9ration Hospitalo-Universitaire, 67085 Strasbourg, France"},{"name":"INSERM UMR_S 1109, Immuno-Rhumatologie Mol\u00e9culaire, Centre de Recherche d\u2019Immunologie et d\u2019H\u00e9matologie, 67085 Strasbourg, France"},{"name":"Center for Pediatric and Adolescent Medicine, Division of Pediatric Nephrology, University of Heidelberg, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Choquet","sequence":"additional","affiliation":[{"name":"Imagerie Pr\u00e9clinique\u2014UF6237, P\u00f4le d\u2019Imagerie, H\u00f4pitaux Universitaires de Strasbourg, 67098 Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amira","family":"Sayeh","sequence":"additional","affiliation":[{"name":"Imagerie Pr\u00e9clinique\u2014UF6237, P\u00f4le d\u2019Imagerie, H\u00f4pitaux Universitaires de Strasbourg, 67098 Strasbourg, France"},{"name":"P\u00f4le de M\u00e9decine et Chirurgie Bucco-Dentaires, H\u00f4pitaux Universitaires de Strasbourg, 67091 Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1127-3453","authenticated-orcid":false,"given":"Maria","family":"Bartosova","sequence":"additional","affiliation":[{"name":"Center for Pediatric and Adolescent Medicine, Division of Pediatric Nephrology, University of Heidelberg, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Betti","family":"Schaefer","sequence":"additional","affiliation":[{"name":"Center for Pediatric and Adolescent Medicine, Division of Pediatric Nephrology, University of Heidelberg, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrike","family":"Huegel","sequence":"additional","affiliation":[{"name":"Center for Pediatric and Adolescent Medicine, Division of Pediatric Nephrology, University of Heidelberg, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ga\u00eblle","family":"Aubertin-Kirch","sequence":"additional","affiliation":[{"name":"Medical Image Analysis Center (MIAC AG), 4051 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Healy","sequence":"additional","affiliation":[{"name":"Department of Craniofacial Development and Stem Cell Biology, Dental Institute, King\u2019s College London, London SE1 9RT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6611-1921","authenticated-orcid":false,"given":"Fran\u00e7ois","family":"Severac","sequence":"additional","affiliation":[{"name":"Groupe M\u00e9thodes en Recherche Clinique (GMRC), H\u00f4pital Civil, H\u00f4pitaux Universitaires de Strasbourg, 67000 Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00e9bastien","family":"Rizzo","sequence":"additional","affiliation":[{"name":"INSERM, UMR 1033, Universit\u00e9 de Lyon, 69372 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georges","family":"Boivin","sequence":"additional","affiliation":[{"name":"INSERM, UMR 1033, Universit\u00e9 de Lyon, 69372 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7564-9937","authenticated-orcid":false,"given":"Franz","family":"Schaefer","sequence":"additional","affiliation":[{"name":"Center for Pediatric and Adolescent Medicine, Division of Pediatric Nephrology, University of Heidelberg, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel","family":"Fischbach","sequence":"additional","affiliation":[{"name":"Service de P\u00e9diatrie 1, H\u00f4pital de Hautepierre, H\u00f4pitaux Universitaires de Strasbourg, 67098 Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0578-2529","authenticated-orcid":false,"given":"Justine","family":"Bacchetta","sequence":"additional","affiliation":[{"name":"INSERM, UMR 1033, Universit\u00e9 de Lyon, 69372 Lyon, France"},{"name":"Centre de R\u00e9f\u00e9rence des Maladies R\u00e9nales Rares, Centre de R\u00e9f\u00e9rences des Maladies Rares du Calcium et du Phosphore, Hospices Civils de Lyon, 69500 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seiamak","family":"Bahram","sequence":"additional","affiliation":[{"name":"OMICARE, Centre de Recherche d\u2019Immunologie et d\u2019H\u00e9matologie, F\u00e9d\u00e9ration Hospitalo-Universitaire, 67085 Strasbourg, France"},{"name":"INSERM UMR_S 1109, Immuno-Rhumatologie Mol\u00e9culaire, Centre de Recherche d\u2019Immunologie et d\u2019H\u00e9matologie, 67085 Strasbourg, France"},{"name":"Plateforme GENOMAX, Laboratoire d\u2019Immuno-Rhumatologie Mol\u00e9culaire, INSERM UMR_S1109, LabEx Transplantex, Centre de Recherche d\u2019Immunologie et d\u2019H\u00e9matologie, Facult\u00e9 de M\u00e9decine, FMTS, Universit\u00e9 de Strasbourg, 67085 Strasbourg, France"},{"name":"INSERM Franco-Japanese Nextgen HLA Laboratory, 67085 Strasbourg, France"},{"name":"Laboratoire Central d\u2019Immunologie, Plateau Technique de Biologie, P\u00f4le de Biologie, Nouvel H\u00f4pital Civil, 67091 Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4487-3332","authenticated-orcid":false,"given":"Claus Peter","family":"Schmitt","sequence":"additional","affiliation":[{"name":"Center for Pediatric and Adolescent Medicine, Division of Pediatric Nephrology, University of Heidelberg, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,8]]},"reference":[{"key":"ref_1","unstructured":"De Groot, L.J., Chrousos, G., Dungan, K., Feingold, K.R., Grossman, A., Hershman, J.M., Koch, C., Korbonits, M., McLachlan, R., and New, M. 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