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Portal-Nunez S.,Fundacion Jimenez Diaz Capio Group | Lozano D.,Fundacion Jimenez Diaz Capio Group | Fernandez de Castro L.,Fundacion Jimenez Diaz Capio Group | de Gortazar A.R.,University of San Pablo - CEU | And 2 more authors.
FEBS Letters | Year: 2010

Type 1 diabetes mellitus (T1D) is associated with bone loss. Given that the Wnt/β-catenin pathway is a major regulator of bone accrual, we assessed this pathway in mice with streptozotozin-induced T1D. In diabetic mouse long bones, we found alterations favouring the suppression of this pathway by using PCR arrays and β-catenin immunostaining. Downregulation of sclerostin, an inhibitor of this pathway, also occurred, and related to increased osteocyte apoptosis. Our data show that both N- and C-terminal parathyroid hormone-related peptide fragments might exert osteogenic effects in this setting by targeting several genes of this pathway and increasing β-catenin in osteoblastic cells. © 2010 Federation of European Biochemical Societies.


Lozano D.,Fundacion Jimenez Diaz Capio Group | Manzano M.,Complutense University of Madrid | Doadrio J.C.,Complutense University of Madrid | Salinas A.J.,Complutense University of Madrid | And 3 more authors.
Acta Biomaterialia | Year: 2010

Parathyroid hormone-related protein (PTHrP) is an important regulator of bone remodeling. Recent studies show that this protein can induce osteogenic features through its N- and C-terminal domains. Silica-based ordered mesoporous bioceramics with an SBA-15 structure - known to be bioactive and biocompatible - have recently been evaluated for their capacity to uptake and deliver L-tryptophan. This amino acid corresponds to the end position of the 107-111 domain (called osteostatin) of the native C-terminal PTHrP (107-139) fragment, whose true action in bone metabolism is still ill-defined. In the present study, we assessed some effects of the aforementioned biomaterials pressed into disks, loaded or not with osteostatin, in osteoblastic cell cultures. Our data demonstrate that both unmodified and organically modified SBA-15 loaded with this peptide increase cell growth and the expression of several osteoblastic products (alkaline phosphatase, osteocalcin, collagen, osteoprotegerin, receptor activator of nuclear factor-κB ligand and vascular endothelial growth factor) in osteoblastic cells. These findings support the notion that osteostatin coating confers osteogenic features to silica-based ordered mesoporous materials, which make them suitable biomaterials for bone repair. © 2009 Acta Materialia Inc.


Jurado S.,Autonomous University of Barcelona | Garcia-Giralt N.,Autonomous University of Barcelona | Diez-Perez A.,Autonomous University of Barcelona | Esbrit P.,Fundacion Jimenez Diaz Capio Group | And 13 more authors.
Journal of Cellular Biochemistry | Year: 2010

The RANKL/RANK/OPG pathway is essential for bone remodeling regulation. Many hormones and cytokines are involved in regulating gene expression in most of the pathway components. Moreover, any deregulation of this pathway can alter bone metabolism, resulting in loss or gain of bone mass. Whether osteoblasts from osteoporotic and nonosteoporotic patients respond differently to cytokines is unknown. The aim of this study was to compare the effect of interleukin (IL)-1β, proftaglandin E2 (PGE2), and transforming growth factor-β1 (TGF-β1) treatments on OPG and RANKL gene expression in normal (n = 11) and osteoporotic (n = 8) primary osteoblasts. OPG and RANKL mRNA levels of primary human osteoblastic (hOB) cell cultures were assessed by real-time PCR. In all cultures, OPG mRNA increased significantly in response to IL-1β treatment and decreased in response to TGF-β1 whereas PGE 2 treatment had no effect. RANKL mRNA levels were significantly increased by all treatments. Differences in OPG and RANKL responses were observed between osteoporotic and nonosteoporotic hOB: in osteoporotic hOB, the OPG response to IL-1β treatment was up to three times lower (P = 0.009), whereas that of RANKL response to TGF-b1 was five times higher (P = 0.002) after 8 h of treatment, as compared with those in nonosteoporotic hOBs. In conclusion, osteoporotic hOB cells showed an anomalous response under cytokine stimulation, consistent with an enhanced osteoclastogenesis resulting in high levels of bone resorption. © 2010 Wiley-Liss, Inc.


PubMed | Fundacion Jimenez Diaz Capio Group
Type: Journal Article | Journal: Acta biomaterialia | Year: 2010

Parathyroid hormone-related protein (PTHrP) is an important regulator of bone remodeling. Recent studies show that this protein can induce osteogenic features through its N- and C-terminal domains. Silica-based ordered mesoporous bioceramics with an SBA-15 structure - known to be bioactive and biocompatible - have recently been evaluated for their capacity to uptake and deliver L-tryptophan. This amino acid corresponds to the end position of the 107-111 domain (called osteostatin) of the native C-terminal PTHrP (107-139) fragment, whose true action in bone metabolism is still ill-defined. In the present study, we assessed some effects of the aforementioned biomaterials pressed into disks, loaded or not with osteostatin, in osteoblastic cell cultures. Our data demonstrate that both unmodified and organically modified SBA-15 loaded with this peptide increase cell growth and the expression of several osteoblastic products (alkaline phosphatase, osteocalcin, collagen, osteoprotegerin, receptor activator of nuclear factor-kappaB ligand and vascular endothelial growth factor) in osteoblastic cells. These findings support the notion that osteostatin coating confers osteogenic features to silica-based ordered mesoporous materials, which make them suitable biomaterials for bone repair.


Type 1 diabetes mellitus (T1D) is associated with bone loss. Given that the Wnt/beta-catenin pathway is a major regulator of bone accrual, we assessed this pathway in mice with streptozotozin-induced T1D. In diabetic mouse long bones, we found alterations favouring the suppression of this pathway by using PCR arrays and beta-catenin immunostaining. Downregulation of sclerostin, an inhibitor of this pathway, also occurred, and related to increased osteocyte apoptosis. Our data show that both N- and C-terminal parathyroid hormone-related peptide fragments might exert osteogenic effects in this setting by targeting several genes of this pathway and increasing beta-catenin in osteoblastic cells.

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