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PTH receptor signaling in osteocytes governs periosteal bone formation and intracortical remodeling

Authors
 Yumie Rhee  ;  Matthew R Allen  ;  Keith Condon  ;  Virginia Lezcano  ;  Ana C Ronda  ;  Carlo Galli  ;  Naomi Olivos  ;  Giovanni Passeri  ;  Charles A O’Brien  ;  Nicoletta Bivi  ;  Lilian I Plotkin  ;  Teresita Bellido 
Citation
 JOURNAL OF BONE AND MINERAL RESEARCH, Vol.26(5) : 1035-1046, 2011 
Journal Title
JOURNAL OF BONE AND MINERAL RESEARCH
ISSN
 0884-0431 
Issue Date
2011
MeSH
Animals ; Biomarkers/metabolism ; BoneRemodeling/physiology* ; BoneResorption/metabolism ; BoneResorption/pathology ; Cytokines/metabolism ; Extracellular Matrix Proteins/metabolism ; Glycoproteins/metabolism ; LDL-ReceptorRelated Proteins/metabolism ; Low Density LipoproteinReceptor-Related Protein-5 ; Mice ; Mice, Transgenic ; Organ Size ; Osteoblasts/metabolism ; Osteoblasts/pathology ; Osteoclasts/metabolism ; Osteoclasts/pathology ; Osteocytes/metabolism* ; Osteogenesis/physiology* ; Periosteum/pathology ; Periosteum/physiology* ; Phenotype ; Receptor, Parathyroid Hormone, Type 1/metabolism* ; Signal Transduction* ; Skull/metabolism ; Wnt Proteins/metabolism
Keywords
OSTEOCYTES ; PTH RECEPTOR ; PERIOSTEAL BONE FORMATION ; WNT SIGNALING ; INTRACORTICAL REMODELING
Abstract
The periosteal and endocortical surfaces of cortical bone dictate the geometry and overall mechanical properties of bone. Yet the cellular and molecular mechanisms that regulate activity on these surfaces are far from being understood. Parathyroid hormone (PTH) has profound effects in cortical bone, stimulating periosteal expansion and at the same time accelerating intracortical bone remodeling. We report herein that transgenic mice expressing a constitutive active PTH receptor in osteocytes (DMP1-caPTHR1 mice) exhibit increased cortical bone area and an elevated rate of periosteal and endocortical bone formation. In addition, DMP1-caPTHR1 mice display a marked increase in intracortical remodeling and cortical porosity. Crossing DMP1-caPTHR1 mice with mice lacking the Wnt coreceptor, LDL-related receptor 5 (LRP5), or with mice overexpressing the Wnt antagonist Sost in osteocytes (DMP1-Sost mice) reduced or abolished, respectively, the increased cortical bone area, periosteal bone formation rate, and expression of osteoblast markers and Wnt target genes exhibited by the DMP1-caPTHR1 mice. In addition, DMP1-caPTHR1 lacking LRP5 or double transgenic DMP1-caPTHR1;DMP1-Sost mice exhibit exacerbated intracortical remodeling and increased osteoclast numbers, and markedly decreased expression of the RANK decoy receptor osteoprotegerin. Thus, whereas Sost downregulation and the consequent Wnt activation is required for the stimulatory effect of PTH receptor signaling on periosteal bone formation, the Wnt-independent increase in osteoclastogenesis induced by PTH receptor activation in osteocytes overrides the effect on Sost. These findings demonstrate that PTH receptor signaling influences cortical bone through actions on osteocytes and defines the role of Wnt signaling in PTH receptor action
Files in This Item:
T201103252.pdf Download
DOI
10.1002/jbmr.304
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Rhee, Yumie(이유미) ORCID logo https://orcid.org/0000-0003-4227-5638
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/94095
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