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

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

Research output: Contribution to journalArticle

121 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1035-1046
Number of pages12
JournalJournal of Bone and Mineral Research
Volume26
Issue number5
DOIs
Publication statusPublished - 2011 May 1

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Parathyroid Hormone Receptor Type 1
Osteocytes
Osteogenesis
LDL Receptors
Osteoprotegerin
Bone Remodeling
Porosity
Osteoclasts
Parathyroid Hormone
Osteoblasts
Transgenic Mice
Down-Regulation
Cortical Bone
Bone and Bones

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine

Cite this

Rhee, Yumie ; Allen, Matthew R. ; Condon, Keith ; Lezcano, Virginia ; Ronda, Ana C. ; Galli, Carlo ; Olivos, Naomi ; Passeri, Giovanni ; O'Brien, Charles A. ; Bivi, Nicoletta ; Plotkin, Lilian I. ; Bellido, Teresita. / PTH receptor signaling in osteocytes governs periosteal bone formation and intracortical remodeling. In: Journal of Bone and Mineral Research. 2011 ; Vol. 26, No. 5. pp. 1035-1046.
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Rhee, Y, Allen, MR, Condon, K, Lezcano, V, Ronda, AC, Galli, C, Olivos, N, Passeri, G, O'Brien, CA, Bivi, N, Plotkin, LI & Bellido, T 2011, 'PTH receptor signaling in osteocytes governs periosteal bone formation and intracortical remodeling', Journal of Bone and Mineral Research, vol. 26, no. 5, pp. 1035-1046. https://doi.org/10.1002/jbmr.304

PTH receptor signaling in osteocytes governs periosteal bone formation and intracortical remodeling. / Rhee, Yumie; Allen, Matthew R.; Condon, Keith; Lezcano, Virginia; Ronda, Ana C.; Galli, Carlo; Olivos, Naomi; Passeri, Giovanni; O'Brien, Charles A.; Bivi, Nicoletta; Plotkin, Lilian I.; Bellido, Teresita.

In: Journal of Bone and Mineral Research, Vol. 26, No. 5, 01.05.2011, p. 1035-1046.

Research output: Contribution to journalArticle

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AU - Rhee, Yumie

AU - Allen, Matthew R.

AU - Condon, Keith

AU - Lezcano, Virginia

AU - Ronda, Ana C.

AU - Galli, Carlo

AU - Olivos, Naomi

AU - Passeri, Giovanni

AU - O'Brien, Charles A.

AU - Bivi, Nicoletta

AU - Plotkin, Lilian I.

AU - Bellido, Teresita

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