Preserved bone mass in ovariectomized rats treated with parathyroid-hormone-related peptide (1-34) and (107-111) fragments

Rouffet, J.; Coxam, Véronique; Gaumet, N.; Barlet, J.P.

doi:10.1051/rnd:19940508

Cited by 17 publications

(17 citation statements)

References 20 publications

(25 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In any event, the true role of this C-terminal PTHrP domain in bone is unclear. An early study showed that daily administration of osteostatin for 2 weeks to ovariectomized rats prevented bone loss in femur and tibia, apparently at the expense of a positive effect in cortical bone [4]. Very recently, we found that an equivalent dose of PTHrP (107e139) than that used for osteostatin in the latter study reversed the cortical bone loss and improved bone regeneration after marrow ablation in mice undergoing 3-methylprednisolone administration [21].…”

Section: Introductionmentioning

confidence: 63%

The osteoinductive properties of mesoporous silicate coated with osteostatin in a rabbit femur cavity defect model

et al. 2010

View full text Add to dashboard Cite

Section: Introductionmentioning

confidence: 63%

The osteoinductive properties of mesoporous silicate coated with osteostatin in a rabbit femur cavity defect model

et al. 2010

View full text Add to dashboard Cite

“…Moreover, a histomorphometric study in osteopenic rats treated daily for about 2 weeks with PTHrP (107-111), which accounts for the effects of PTHrP (107-139) in various cell types (11,13,15,17,(43)(44)(45), found a decreased trabecular bone formation associated with an increased bone resorption (46). Because, as stated above, NF-B activation appears to be a common mechanism of bone resorption activators in osteoblastic cells, our present findings further support that PTHrP (107-139) might be a stimulator of bone resorption.…”

Section: Discussionmentioning

confidence: 99%

Both N- and C-terminal Domains of Parathyroid Hormone-related Protein Increase Interleukin-6 by Nuclear Factor-κB Activation in Osteoblastic Cells

Guillén¹,

Martı́nez²,

Gortázar³

et al. 2002

Journal of Biological Chemistry

View full text Add to dashboard Cite

Parathyroid hormone (PTH)-related protein (PTHrP) seems to affect bone resorption by interaction with bone cytokines, among them interleukin-6 (IL-6). Recent studies suggest that nuclear factor (NF)-B activation has an important role in bone resorption. We assessed whether the N-terminal fragment of PTHrP, and its C-terminal region, unrelated to PTH, can activate NF-B, and its relationship with IL-6 gene induction in different rat and human osteoblastic cell preparations. Here we present molecular data demonstrating that both PTHrP (1-36) and PTHrP (107-139) activate NF-B, leading to an increase in IL-6 mRNA, in these cells. Using anti-p65 and anti-p50 antibodies, we detected the presence of both proteins in the activated NF-B complex. This effect induced by either the N-or C-terminal PTHrP domain in osteoblastic cells appears to occur by different intracellular mechanisms, involving protein kinase A or intracellular Ca 2؉ /protein kinase C activation, respectively. However, the effect of each peptide alone did not increase further when added together. Our findings lend support to the hypothesis that the C-terminal domain of PTHrP, in a manner similar to its N-terminal fragment, might stimulate bone resorption. These studies also provide further insights into the putative role of PTHrP as a modulator of bone remodeling.

show abstract

“…The N‐terminal domain of PTHrP interacts with the PTH 1 receptor (PTH 1 R) in osteoblasts (Dean et al ., 2008). As shown to be the case with PTH, this domain is anabolic for bone when administered in an intermittent manner (Rouffet et al ., 1994; Stewart et al ., 2000; Horwitz et al ., 2003; Goltzman, 2008; Lozano et al ., 2009). In addition, recent studies strongly suggest that PTHrP domains other than its N‐terminal domain might contribute to the PTHrP role(s) in bone.…”

Section: Introductionmentioning

confidence: 95%

The C‐terminal fragment of parathyroid hormone‐related peptide promotes bone formation in diabetic mice with low‐turnover osteopaenia

Lozano

Fernández-de-Castro

Portal‐Núñez

et al. 2011

British J Pharmacology

View full text Add to dashboard Cite

BACKGROUND AND PURPOSECurrent data suggest that parathyroid hormone (PTH)-related peptide (PTHrP) domains other than the N-terminal PTH-like domain contribute to its role as an endogenous bone anabolic factor. PTHrP-107-139 inhibits bone resorption, a fact which has precluded an unequivocal demonstration of its possible anabolic action in vivo. We thus sought to characterize the osteogenic effects of this peptide using a mouse model of diabetic low-turnover osteopaenia. EXPERIMENTAL APPROACHPTHrP-107-139 was administered to streptozotocin-induced diabetic mice, with or without bone marrow ablation, for 13 days. Osteopaenia was confirmed by dual-energy X-ray absorptiometry and microcomputed tomography analysis. Histological analysis was performed on paraffin-embedded bone tissue sections by haematoxylin/eosin and Masson's staining, and tartrate-resistent acid phosphatase immunohistochemistry. Mouse bone marrow stromal cells and osteoblastic MC3T3-E1 cells were cultured in normal and/or high glucose (HG) medium. Osteogenic and adipogenic markers were assessed by real-time PCR, and PTHrP and the PTH1 receptor protein expression by Western blot analysis. KEY RESULTSPTHrP-107-139 reversed the alterations in bone structure and osteoblast function, and also promoted bone healing after marrow ablation without affecting the number of osteoclast-like cells in diabetic mice. This peptide also reversed the high-glucose-induced changes in osteogenic differentiation in both bone marrow stromal cells and the more differentiated MC3T3-E1 cells. CONCLUSIONS AND IMPLICATIONSThese findings demonstrate that PTHrP-107-139 promotes bone formation in diabetic mice. This mouse model and in vitro cell cultures allowed us to identify various anabolic effects of this peptide in this scenario. AbbreviationsmCT, microcomputed tomography; ALP, alkaline phosphatase; BMC, bone marrow cells; BMD, bone mineral density; DXA, dual-energy X-ray absorptiometry; FABP, adipocyte fatty acid-binding protein; NLS, nuclear localization signal; OC, osteocalcin; OPG, osteoprotegerin; PPARg2, peroxisome proliferator-activated receptor; PTH, parathyroid hormone; PTHrP, parathyroid hormone-related protein; PTH1R, parathyroid hormone receptor 1; STZ, streptozotozin; TNFRSF11A, receptor activator of nuclear factor-kb ligand; TRAP, tartrate-resistant acid phosphatase; VEGF, vascular endothelial growth factor BJP British Journal of Pharmacology

show abstract

Preserved bone mass in ovariectomized rats treated with parathyroid-hormone-related peptide (1-34) and (107-111) fragments

Cited by 17 publications

References 20 publications

The osteoinductive properties of mesoporous silicate coated with osteostatin in a rabbit femur cavity defect model

The osteoinductive properties of mesoporous silicate coated with osteostatin in a rabbit femur cavity defect model

Both N- and C-terminal Domains of Parathyroid Hormone-related Protein Increase Interleukin-6 by Nuclear Factor-κB Activation in Osteoblastic Cells

The C‐terminal fragment of parathyroid hormone‐related peptide promotes bone formation in diabetic mice with low‐turnover osteopaenia

Contact Info

Product

Resources

About