Calcium fluxes at the bone/plasma interface: Acute effects of parathyroid hormone (PTH) and targeted deletion of PTH/PTH-related peptide (PTHrP) receptor in the osteocytes

C Dedic, TS Hung, AM Shipley, A Maeda, T Gardella, AL Miller, P Divieti Pajevic, JG Kunkel, A Rubinacci

Research output: Contribution to journalArticle

Abstract

Calcium ion concentration ([Ca2+]) in the systemic extracellular fluid, ECF-[Ca2+], is maintained around a genetically predetermined set-point, which combines the operational level of the kidney and bone/ECF interfaces. The ECF-[Ca2+] is maintained within a narrow oscillation range by the regulatory action of Parathyroid Hormone (PTH), Calcitonin, FGF-23, and 1,25(OH)2D3. This model implies two correction mechanisms, i.e. tubular Ca2+reabsorption and osteoclast Ca2+resorption. Although their alterations have an effect on the ECF-[Ca2+] maintenance, they cannot fully account for rapid correction of the continuing perturbations of plasma [Ca2+], which occur daily in life. The existence of Ca2+fluxes at quiescent bone surfaces fulfills the role of a short-term error correction mechanism in Ca2+homeostasis. To explore the hypothesis that PTH regulates the cell system responsible for the fast Ca2+fluxes at the bone/ECF interface, we have performed direct real-time measurements of Ca2+fluxes at the surface of ex-vivo metatarsal bones maintained in physiological conditions mimicking ECF, and exposed to PTH. To further characterize whether the PTH receptor on osteocytes is a critical component of the minute-to-minute ECF-[Ca2+] regulation, metatarsal bones from mice lacking the PTH receptor in these cells were tested ex vivo for rapid Ca2+exchange. We performed direct real-time measurements of Ca2+fluxes and concentration gradients by a scanning ion-selective electrode technique (SIET). To validate ex vivo measurements, we also evaluated acute calcemic response to PTH in vivo in mice lacking PTH receptors in osteocytes vs littermate controls. Our data demonstrated that Ca2+fluxes at the bone-ECF interface in excised bones as well as acute calcemic response in the short-term were unaffected by PTH exposure and its signaling through its receptor in osteocytes. Rapid minute-to-minute regulation of the ECF-[Ca2+] was found to be independent of PTH actions on osteocytes. Similarly, mice lacking PTH receptor in osteocytes, responded to PTH challenge with similar calcemic increases. © 2018 Elsevier Inc.
Original languageEnglish
Pages (from-to)135-143
Number of pages9
JournalBone
Volume116
DOIs
Publication statusPublished - 2018

Fingerprint

Parathyroid Hormone Receptor Type 1
Osteocytes
Parathyroid Hormone
Calcium
Bone and Bones
Metatarsal Bones
Parathyroid Hormone Receptors
Ion-Selective Electrodes
Fibroblast Growth Factor 1
Extracellular Fluid
Calcitonin
Osteoclasts
Homeostasis
Maintenance
Ions
Kidney

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Calcium fluxes at the bone/plasma interface: Acute effects of parathyroid hormone (PTH) and targeted deletion of PTH/PTH-related peptide (PTHrP) receptor in the osteocytes. / Dedic, C; Hung, TS; Shipley, AM; Maeda, A; Gardella, T; Miller, AL; Divieti Pajevic, P; Kunkel, JG; Rubinacci, A.

In: Bone, Vol. 116, 2018, p. 135-143.

Research output: Contribution to journalArticle

Dedic, C ; Hung, TS ; Shipley, AM ; Maeda, A ; Gardella, T ; Miller, AL ; Divieti Pajevic, P ; Kunkel, JG ; Rubinacci, A. / Calcium fluxes at the bone/plasma interface: Acute effects of parathyroid hormone (PTH) and targeted deletion of PTH/PTH-related peptide (PTHrP) receptor in the osteocytes. In: Bone. 2018 ; Vol. 116. pp. 135-143.
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abstract = "Calcium ion concentration ([Ca2+]) in the systemic extracellular fluid, ECF-[Ca2+], is maintained around a genetically predetermined set-point, which combines the operational level of the kidney and bone/ECF interfaces. The ECF-[Ca2+] is maintained within a narrow oscillation range by the regulatory action of Parathyroid Hormone (PTH), Calcitonin, FGF-23, and 1,25(OH)2D3. This model implies two correction mechanisms, i.e. tubular Ca2+reabsorption and osteoclast Ca2+resorption. Although their alterations have an effect on the ECF-[Ca2+] maintenance, they cannot fully account for rapid correction of the continuing perturbations of plasma [Ca2+], which occur daily in life. The existence of Ca2+fluxes at quiescent bone surfaces fulfills the role of a short-term error correction mechanism in Ca2+homeostasis. To explore the hypothesis that PTH regulates the cell system responsible for the fast Ca2+fluxes at the bone/ECF interface, we have performed direct real-time measurements of Ca2+fluxes at the surface of ex-vivo metatarsal bones maintained in physiological conditions mimicking ECF, and exposed to PTH. To further characterize whether the PTH receptor on osteocytes is a critical component of the minute-to-minute ECF-[Ca2+] regulation, metatarsal bones from mice lacking the PTH receptor in these cells were tested ex vivo for rapid Ca2+exchange. We performed direct real-time measurements of Ca2+fluxes and concentration gradients by a scanning ion-selective electrode technique (SIET). To validate ex vivo measurements, we also evaluated acute calcemic response to PTH in vivo in mice lacking PTH receptors in osteocytes vs littermate controls. Our data demonstrated that Ca2+fluxes at the bone-ECF interface in excised bones as well as acute calcemic response in the short-term were unaffected by PTH exposure and its signaling through its receptor in osteocytes. Rapid minute-to-minute regulation of the ECF-[Ca2+] was found to be independent of PTH actions on osteocytes. Similarly, mice lacking PTH receptor in osteocytes, responded to PTH challenge with similar calcemic increases. {\circledC} 2018 Elsevier Inc.",
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T1 - Calcium fluxes at the bone/plasma interface: Acute effects of parathyroid hormone (PTH) and targeted deletion of PTH/PTH-related peptide (PTHrP) receptor in the osteocytes

AU - Dedic, C

AU - Hung, TS

AU - Shipley, AM

AU - Maeda, A

AU - Gardella, T

AU - Miller, AL

AU - Divieti Pajevic, P

AU - Kunkel, JG

AU - Rubinacci, A

PY - 2018

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N2 - Calcium ion concentration ([Ca2+]) in the systemic extracellular fluid, ECF-[Ca2+], is maintained around a genetically predetermined set-point, which combines the operational level of the kidney and bone/ECF interfaces. The ECF-[Ca2+] is maintained within a narrow oscillation range by the regulatory action of Parathyroid Hormone (PTH), Calcitonin, FGF-23, and 1,25(OH)2D3. This model implies two correction mechanisms, i.e. tubular Ca2+reabsorption and osteoclast Ca2+resorption. Although their alterations have an effect on the ECF-[Ca2+] maintenance, they cannot fully account for rapid correction of the continuing perturbations of plasma [Ca2+], which occur daily in life. The existence of Ca2+fluxes at quiescent bone surfaces fulfills the role of a short-term error correction mechanism in Ca2+homeostasis. To explore the hypothesis that PTH regulates the cell system responsible for the fast Ca2+fluxes at the bone/ECF interface, we have performed direct real-time measurements of Ca2+fluxes at the surface of ex-vivo metatarsal bones maintained in physiological conditions mimicking ECF, and exposed to PTH. To further characterize whether the PTH receptor on osteocytes is a critical component of the minute-to-minute ECF-[Ca2+] regulation, metatarsal bones from mice lacking the PTH receptor in these cells were tested ex vivo for rapid Ca2+exchange. We performed direct real-time measurements of Ca2+fluxes and concentration gradients by a scanning ion-selective electrode technique (SIET). To validate ex vivo measurements, we also evaluated acute calcemic response to PTH in vivo in mice lacking PTH receptors in osteocytes vs littermate controls. Our data demonstrated that Ca2+fluxes at the bone-ECF interface in excised bones as well as acute calcemic response in the short-term were unaffected by PTH exposure and its signaling through its receptor in osteocytes. Rapid minute-to-minute regulation of the ECF-[Ca2+] was found to be independent of PTH actions on osteocytes. Similarly, mice lacking PTH receptor in osteocytes, responded to PTH challenge with similar calcemic increases. © 2018 Elsevier Inc.

AB - Calcium ion concentration ([Ca2+]) in the systemic extracellular fluid, ECF-[Ca2+], is maintained around a genetically predetermined set-point, which combines the operational level of the kidney and bone/ECF interfaces. The ECF-[Ca2+] is maintained within a narrow oscillation range by the regulatory action of Parathyroid Hormone (PTH), Calcitonin, FGF-23, and 1,25(OH)2D3. This model implies two correction mechanisms, i.e. tubular Ca2+reabsorption and osteoclast Ca2+resorption. Although their alterations have an effect on the ECF-[Ca2+] maintenance, they cannot fully account for rapid correction of the continuing perturbations of plasma [Ca2+], which occur daily in life. The existence of Ca2+fluxes at quiescent bone surfaces fulfills the role of a short-term error correction mechanism in Ca2+homeostasis. To explore the hypothesis that PTH regulates the cell system responsible for the fast Ca2+fluxes at the bone/ECF interface, we have performed direct real-time measurements of Ca2+fluxes at the surface of ex-vivo metatarsal bones maintained in physiological conditions mimicking ECF, and exposed to PTH. To further characterize whether the PTH receptor on osteocytes is a critical component of the minute-to-minute ECF-[Ca2+] regulation, metatarsal bones from mice lacking the PTH receptor in these cells were tested ex vivo for rapid Ca2+exchange. We performed direct real-time measurements of Ca2+fluxes and concentration gradients by a scanning ion-selective electrode technique (SIET). To validate ex vivo measurements, we also evaluated acute calcemic response to PTH in vivo in mice lacking PTH receptors in osteocytes vs littermate controls. Our data demonstrated that Ca2+fluxes at the bone-ECF interface in excised bones as well as acute calcemic response in the short-term were unaffected by PTH exposure and its signaling through its receptor in osteocytes. Rapid minute-to-minute regulation of the ECF-[Ca2+] was found to be independent of PTH actions on osteocytes. Similarly, mice lacking PTH receptor in osteocytes, responded to PTH challenge with similar calcemic increases. © 2018 Elsevier Inc.

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