Comparison of bone formation responses to parathyroid hormone(1-34), (1-31), and (2-34) in mice

Mohan, Subburaman; Kutı́lek, Štěpán; Zhang, C; Shen, Huawei; Kodama, Y.; Srivastava, Apurva K.; Wergedal, Jon E.; Beamer, Wesley G.; Baylink, David J.

doi:10.1016/s8756-3282(00)00355-0

Cited by 95 publications

(84 citation statements)

References 51 publications

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“…It also may inhibit apoptosis in mature osteoblasts, which might prolong the anabolic effects of PTH. (12)(13)(14)(15)(16)(17)(18)(19)30) However, to fully appreciate the responses of bone to PTH, it is also necessary to understand how PTH administration affects other type of cells in the bone microenvironment that are implicated in bone turnover. Osteoclasts are another potential target of PTH action because the physiologic activities of osteoblasts and osteoclasts are tightly coupled.…”

Section: Discussionmentioning

confidence: 99%

“…Continuous administration of PTH induces catabolic effects on bone, whereas intermittent PTH administration exerts anabolic effects. (12)(13)(14)(15)(16)(17)(18)(19) Currently, once-daily injection of human PTH is approved by the Food and Drug Administration as treatment for osteoporosis in the United States. In addition, it could have potential for the treatment of other conditions that require new bone formation.…”

Section: Introductionmentioning

confidence: 99%

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Parathyroid hormone regulates the distribution and osteoclastogenic potential of hematopoietic progenitors in the bone marrow

Jacome-Galarza

Lee

Lorenzo

et al. 2010

Journal of Bone and Mineral Research

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Parathyroid hormone (PTH) increases both the number of osteoclast in bone and the number of early hematopoietic stem cells (HSCs) in bone marrow. We previously characterized the phenotype of multiple populations of bone marrow cells with in vitro osteoclastogenic potential in mice. Here we examined whether intermittent administration of PTH influences these osteoclast progenitor (OCP) populations. C57BL/6 mice were treated with daily injections of bPTH(1-34) (80 mg/kg/day) for 7 or 14 days. We found that PTH caused a significant increase in the percentage of TN/CD115 þ CD117 high and TN/CD115 þ CD117 int cells ( p < .05) in bone marrow on day 7. In contrast, PTH decreased the absolute number of TN/CD115 þ CD117 low cells by 39% on day 7 ( p < .05). On day 14, there was no effect of PTH on osteoclast progenitor distribution in vivo. However, PTH treatment for 7 and 14 days did increase receptor activator of NF-kB ligand (RANKL)-and macrophage colony-stimulating factor (M-CSF)-stimulated in vitro osteoclastogenesis and bone resorption in TN/ CD115 þ cells. In the periphery, 14 days of treatment increased the percentage and absolute numbers of HSCs (Lin À CD117 þ Sca-1 þ ) in the spleen ( p < .05). These data correlated with an increase in the percent and absolute numbers of HSCs in bone marrow on day 14 ( p < .05). Interestingly, the effects on hematopoietic progenitors do not depend on osteoclast resorption activity. These results suggest that in vivo PTH treatment increased in vitro osteoclastogenesis and resorption without altering the number of osteoclast precursors. This implies that in vivo PTH induces sustained changes, possibly through an epigenetic mechanism, in the in vitro responsiveness of the cells to M-CSF and RANKL. ß

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Parathyroid hormone regulates the distribution and osteoclastogenic potential of hematopoietic progenitors in the bone marrow

Jacome-Galarza

Lee

Lorenzo

et al. 2010

Journal of Bone and Mineral Research

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“…In the majority of studies, intermittent PTH 1-34 administration consistently enhances trabecular bone formation in the femur; however, responses are more variable in the lumbar spine and tibia [10,12,13,18]. Previous studies suggest, initial trabecular volume of skeletal sites and animal age are important considerations when investigating the bone anabolic effect of PTH in murine models [10,11,13,17,18,25].…”

Section: Experimental Designmentioning

confidence: 99%

“…The anabolic action of intermittent PTH 1-34 on the skeleton has been studied widely in rodent models [10][11][12][13][14][15][16][17]. Studies employing murine models suggest the skeletal response to exogenous PTH 1-34 varies depending on the dose and duration of administration, as well as the mouse strain, age, and skeletal site investigated.…”

mentioning

confidence: 99%

“…Studies employing murine models suggest the skeletal response to exogenous PTH 1-34 varies depending on the dose and duration of administration, as well as the mouse strain, age, and skeletal site investigated. Investigations of PTH 1-34 action on bone have employed doses ranging from 3-800 μg/ kg of body weight [10,11,[13][14][15][17][18][19] and durations lasting a couple of weeks to several months [14,[18][19][20][21][22]. In general, low dose (≤ 40 µg/kg), short term (≤ 3 weeks) intermittent PTH 1-34 administration enhances bone formation without altering bone resorp-Enzyme-linked immunosorbent assay kits for serum osteocalcin, mouse specific tartrate resistant acid phosphatase 5b (TRACP-5b), and type I collagen teleopeptides were purchased from Biomedical Technologies Inc. (Stoughton, MA), Immunodiagnostics Systems Inc. (Fountain Hills, AZ), and Nordic Bioscience Diagnostics (Herlev, Denmark), respectively.…”

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confidence: 99%

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Short-term intermittent PTH 1-34 administration enhances bone formation in SCID/Beige mice

et al. 2010

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Parathyroid hormone (Pth) is an 84 amino acid polypeptide secreted by parathyroid glands in response to low serum calcium. The exogenous administration of PTH can induce both anabolic and catabolic actions in bone; however, such consequences depend upon how PTH is administered. Continuous PTH infusion, similar to the condition of hyperparathyroidism, initiates bone catabolism by enhancing resorption and decreasing formation. In contrast, when administered intermittently (by daily injection), PTH promotes bone formation, as measured by increased bone mass and enhanced mechanical properties [1][2][3][4][5] abstract. The anabolic effect of intermittent PTH on bone is variable depending on the species studied, duration/mode of administration, and location of skeletal response investigated. We tested the hypothesis that low dose, short term, intermittent PTH 1-34 administration is sufficient to enhance bone formation without altering bone resorption. To test our hypothesis, mice were treated intermittently with one of three concentrations of PTH 1-34 (1 μg/kg, low; 10 μg/kg or 20 μg/kg, high) for three weeks. The skeletal response was identified by quantifying: serum markers of bone turnover, cancellous bone parameters in distal femur, proximal tibia, and lumbar vertebrae by µCT, and number of osteoblasts and osteoclasts in distal femur. Mice receiving 20 μg/kg of PTH 1-34 demonstrated a 30% increase in serum osteocalcin, but no differences in serum calcium, type I collagen teleopeptides, or TRACP 5b. For all bones, µCT analysis suggested mice receiving 20 μg/kg of PTH 1-34 had increased cancellous bone mineral density, trabecular thickness and spacing, but decreased trabecular number. A 60% increase in the number of alkaline phosphatase positive osteoblasts in the distal femur was also observed in tissue sections; however, the number of TRAP positive osteoclasts was not different between test and control groups. While animals administered 10 μg/kg demonstrated similar trends for all bone turnover indices, such alterations were not observed in animals administered PTH 1-34 at 1 μg/kg per day. Thus, PTH 1-34, administered intermittently for three weeks at 20 μg/kg is sufficient to enhance bone formation without enhancing resorption.Key words: Parathyroid hormone, Bone turnover, SCID/Beige mouse, Microcomputed tomography full length peptide, the first 34 amino acids (1-34) are sufficient for its biological activity in bone [3,[6][7][8].Daily PTH 1-34 administration, similar to the full length peptide, is thought to increase bone formation primarily by enhancing the number of bone forming osteoblasts [9]. The anabolic action of intermittent PTH 1-34 on the skeleton has been studied widely in rodent models [10][11][12][13][14][15][16][17]. Studies employing murine models suggest the skeletal response to exogenous PTH 1-34 varies depending on the dose and duration of administration, as well as the mouse strain, age, and skeletal site investigated. Investigations of PTH 1-34 action on bone have employed doses ranging from ...

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Claudin 18 is a novel negative regulator of bone resorption and osteoclast differentiation

Linares

Brommage

Powell

et al. 2012

Journal of Bone and Mineral Research

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Claudin 18 (Cldn-18) belongs to a large family of transmembrane proteins that are important components of tight junction strands. Although several claudin members are expressed in bone, the functional role for any claudin member in bone is unknown. Here we demonstrate that disruption of Cldn-18 in mice markedly decreased total body bone mineral density, trabecular bone volume, and cortical thickness in Cldn-18 −/− mice. Histomorphometric studies revealed that bone resorption parameters were increased significantly in Cldn-18 −/− mice without changes in bone formation. Serum levels of TRAP5b and mRNA expression levels of osteoclast specific markers and signaling molecules were also increased. Loss of Cldn-18 further exacerbated calcium deficiency induced bone loss by influencing bone resorption, thereby resulting in mechanically weaker bone. In vitro studies with bone marrow macrophages revealed Cldn-18 disruption markedly enhanced RANKL-induced osteoclast differentiation but not MCSF-induced BMM proliferation. Consistent with a direct role for Cldn-18 in regulating osteoclast differentiation, overexpression of wild type but not PDZ binding motif deleted Cldn-18 inhibited RANKL-induced osteoclast differentiation. Furthermore, our findings indicate that Cldn-18 interacts with Zonula occludens 2 (ZO-2) to modulate RANKL signaling in osteoclasts. In conclusion, we demonstrate that Cldn-18 is a novel negative regulator of bone resorption and osteoclast differentiation.

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Comparison of bone formation responses to parathyroid hormone(1-34), (1-31), and (2-34) in mice

Cited by 95 publications

References 51 publications

Parathyroid hormone regulates the distribution and osteoclastogenic potential of hematopoietic progenitors in the bone marrow

Parathyroid hormone regulates the distribution and osteoclastogenic potential of hematopoietic progenitors in the bone marrow

Short-term intermittent PTH 1-34 administration enhances bone formation in SCID/Beige mice

Claudin 18 is a novel negative regulator of bone resorption and osteoclast differentiation

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