Administration of PTH-(7-84) Antagonizes the Effects of PTH-(1-84) on Bone in Rats with Moderate Renal Failure

Langub, M. Chris; Monier‐Faugere, Marie‐Claude; Wang, Guodong; Williams, John P.; Koszewski, Nicholas J.; Malluche, Hartmut H.

doi:10.1210/en.2002-221026

Cited by 90 publications

(73 citation statements)

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“…Bears do not urinate during hibernation, and therefore may experience a similar phenomenon. Large C-PTH fragments, acting through a CPTH receptor found on osteoblasts and osteocytes, have an anti-resorptive effect in vitro and a hypocalcaemic effect in vivo [49][50][51]. A possible mechanism for how PTH could explain the cortical bone remodeling observed in the current study is shown in Figure 6.…”

Section: Discussionmentioning

confidence: 71%

Decreased bone turnover with balanced resorption and formation prevent cortical bone loss during disuse (hibernation) in grizzly bears (Ursus arctos horribilis)

McGee

Maki

Johnson

et al. 2008

Bone

102

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Disuse uncouples bone formation from resorption, leading to increased porosity, decreased bone geometrical properties, and decreased bone mineral content which compromises bone mechanical properties and increases fracture risk. However, black bear bone properties are not adversely affected by aging despite annual periods of disuse (i.e., hibernation), which suggests that bears either prevent bone loss during disuse or lose bone and subsequently recover it at a faster rate than other animals. Here we show decreased cortical bone turnover during hibernation with balanced formation and resorption in grizzly bear femurs. Hibernating grizzly bear femurs were less porous and more mineralized, and did not demonstrate any changes in cortical bone geometry or whole bone mechanical properties compared to active grizzly bear femurs. The activation frequency of intracortical remodeling was 75% lower during hibernation than during periods of physical activity, but the normalized mineral apposition rate was unchanged. These data indicate bone turnover decreases during hibernation, but osteons continue to refill at normal rates. There were no changes in regional variation of porosity, geometry, or remodeling indices in femurs from hibernating bears, indicating that hibernation did not preferentially affect one region of the cortex. Thus, grizzly bears prevent bone loss during disuse by decreasing bone turnover and maintaining balanced formation and resorption, which preserves bone structure and strength. These results support the idea that bears possess a biological mechanism to prevent disuse osteoporosis.

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Section: Discussionmentioning

confidence: 71%

Decreased bone turnover with balanced resorption and formation prevent cortical bone loss during disuse (hibernation) in grizzly bears (Ursus arctos horribilis)

McGee

Maki

Johnson

et al. 2008

Bone

102

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“…Thus, the accumulation of PTH (7-84) in renal failure may lead to PTH resistance by internalizing and downregulating PTH receptors without their activation, having an inhibiting net effect on PTH signaling (27). In this study PTH (7-84) treatment of both cell lines frequently exerts antagonistic effects on the regulation of genes related to HA metabolism as compared with PTH (1-34).…”

Section: Discussionmentioning

confidence: 82%

“…In this study PTH (7-84) treatment of both cell lines frequently exerts antagonistic effects on the regulation of genes related to HA metabolism as compared with PTH (1-34). These actions could be due to a non-PTH (1-34)-like effect on the PTH1R, since PTH (7-84) can bind to this receptor, inhibit the action of the N-terminally intact agonists, and induce internalization in some cells (27). Alternatively, signaling of the N-terminal truncated peptides through a novel putative PTH receptor with high affinity binding site for carboxyl terminal PTH peptides has been proposed (7).…”

Section: Discussionmentioning

confidence: 99%

Parathyroid hormone (PTH) peptides through the regulation of hyaluronan metabolism affect osteosarcoma cell migration

et al. 2010

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SummaryParathyroid hormone (PTH) strongly stimulates hyaluronan (HA) synthesis and secretion of both normal and carcinogenic cells of the osteoblastic lineage and improves skeletal microarchitecture. HA, a glycosaminoglycan component of the extracellular matrix (ECM), is capable of transmitting ECM-derived signals to regulate cellular function. In this study, we investigated whether the changes of HA metabolism induced by PTH (1-34) and PTH (7-84) peptides in moderately MG-63 and well-differentiated Saos 2 osteosarcoma cell lines, are correlated to their migration capabilities. Our results demonstrate that intermittent PTH (1-34) treatment significantly (P 0.01) supported the migration of MG-63 cells, increased their HA-synthase-2 (HAS2) expression (P 0.001), and enhanced their high-molecular size HA deposition in the pericellular matrix. Both increased endogenous HA production (P 0.01) and treatment with exogenous high-molecular weight HA (P 0.05) correlated to a significant increase of MG-63 cell migration capacity. Transfection with siHAS2 showed that PTH (1-34), mainly through HAS2, enhanced HA and regulated MG-63 cell motility. Interestingly, continuous PTH (1-34) treatment stimulated both Saos 2 cell HAS2 (P 0.001) and HAS1 (P 0.001) isoform expression inhibited their HYAL2 expression (P 0.001) and modestly (P 0.05) enhanced their migration. Therefore, the PTH (1-34) administration mode appears to distinctly modulate the migratory responses of the MG-63 moderately and Saos 2 well-differentiated osteosarcoma cell lines. Conclusively, the obtained data suggest that there is a regulatory effect of PTH (1-34), in an administration mode-dependent manner, on HA metabolism that is essential for osteosarcoma cell migration.

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“…2 Vascular calcification is very severe in patients with end stage renal disease; phosphate retention and an elevated calcium-phosphate product no doubt contribute to pathophysiology (44). In this setting, however, both skeletal refractoriness to PTH and secondary hyperparathyroidism arise, the former in part because of PTH(7-84), a PTH fragment that antagonizes PTH(1-84) signaling (45). Of note, hypoparathyroidism arising from either congenital (46) or iatrogenic (47) causes appears to increase the risk for cardiovascular calcification.…”

Section: Pth(1-34) and Opn Suppress In Vitro Osteogenic Mineralizatiomentioning

confidence: 99%

Teriparatide (Human Parathyroid Hormone (1–34)) Inhibits Osteogenic Vascular Calcification in Diabetic Low Density Lipoprotein Receptor-deficient Mice

Shao

Cheng

Charlton-Kachigian

et al. 2003

Journal of Biological Chemistry

166

149

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Over a century ago, the pathologist Rudolph Virchow recognized the involvement of calcified tissues in the pathobiology of vascular diseases (1). Coining the term "endarteritis deformans" he descriptively denoted the histological character of the atherosclerotic plaque as exhibiting features of a progressively calcified scar tissue that forms in response to a vascular inflammatory state. Since then, a minimum of three histoanatomic variants of macrovascular calcification, atherosclerosis, calcific valvular sclerosis, and medial artery calcification, have been shown arise in response to metabolic, mechanical, infectious, or inflammatory diseases (2-4). Both early and recent studies point to cellular processes that resemble bone formation at the histological level. However, Demer and co-workers (5) were the first to provide direct evidence for active osteogenic regulation of vascular calcification. They identified BMP2, 1 a powerful bone morphogenetic protein, as a key component of the mineralized atherosclerotic plaque (5). Thus, rather than being a passive process, vascular calcification is in part subject to active regulation. Once thought benign, the deleterious clinical consequences of calcific vasculopathy are now becoming clearer (6 -10). Patients with diabetes have increased mortality and 3-fold increased risk for lower extremity amputation in the setting of medial artery calcification (11). In patients with asymptomatic aortic stenosis, a moderate to severe echocardiographic valve calcification score is the single best predictor of vascular disease progression, again exceeding blood pressure control, lipid control, and diabetes control in positive predictive value (12). Risk for stroke, particularly notable in post-menopausal women, is increased in the presence of aortic arch calcification (13). Multiple metabolic stimuli contribute to calcific vascular disease initiation and progression in patients with diabetes, hypercholesterolemia, poor glycemic control, and phosphate retention associated with renal failure contributing to vascular calcium accumulation (2). A fundamental understanding the molecular physiology of vascular calcification will provide insights useful for developing strategies to prevent and treat this macrovascular disease process.Metabolic contributions to vascular calcification are well known and include hypercholesterolemia, diabetes, hyperphosphatemia, vitamin D toxicosis, magnesium deficiency, and chronic renal insufficiency (2). The mechanisms whereby the metabolic insults of diabetes initiate and propagate vascular calcification are beginning to be examined in detail. Hyperglycemia, hyperlipidemia, and oxidative stress (3, 14) up-regulate the expression of vascular signaling molecules that promote mineral deposition in a process that resembles craniofacial bone formation (15). Hyperglycemia and hyperlipidemia have

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Administration of PTH-(7-84) Antagonizes the Effects of PTH-(1-84) on Bone in Rats with Moderate Renal Failure

Cited by 90 publications

References 0 publications

Decreased bone turnover with balanced resorption and formation prevent cortical bone loss during disuse (hibernation) in grizzly bears (Ursus arctos horribilis)

Decreased bone turnover with balanced resorption and formation prevent cortical bone loss during disuse (hibernation) in grizzly bears (Ursus arctos horribilis)

Parathyroid hormone (PTH) peptides through the regulation of hyaluronan metabolism affect osteosarcoma cell migration

Teriparatide (Human Parathyroid Hormone (1–34)) Inhibits Osteogenic Vascular Calcification in Diabetic Low Density Lipoprotein Receptor-deficient Mice

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