Grassi F.,Laboratorio RAMSES |
Tyagi A.M.,Emory University |
Calvert J.W.,Emory University |
Gambari L.,Laboratorio Of Immunoreumatologia E Rigenerazione Tissutale |
And 8 more authors.
Journal of Bone and Mineral Research
Hydrogen sulfide (H2S) is a gasotransmitter known to regulate bone formation and bone mass in unperturbed mice. However, it is presently unknown whether H2S plays a role in pathologic bone loss. Here we show that ovariectomy (ovx), a model of postmenopausal bone loss, decreases serum H2S levels and the bone marrow (BM) levels of two key H2S-generating enzymes, cystathione β-synthase (CBS) and cystathione γ-lyase (CSE). Treatment with the H2S-donor GYY4137 (GYY) normalizes serum H2S in ovx mice, increases bone formation, and completely prevents the loss of trabecular bone induced by ovx. Mechanistic studies revealed that GYY increases murine osteoblastogenesis by activating Wnt signaling through increased production of the Wnt ligands Wnt16, Wnt2b, Wnt6, and Wnt10b in the BM. Moreover, in vitro treatment with 17β-estradiol upregulates the expression of CBS and CSE in human BM stromal cells (hSCs), whereas an H2S-releasing drug induces osteogenic differentiation of hSCs. In summary, regulation of H2S levels is a novel mechanism by which estrogen stimulates osteoblastogenesis and bone formation in mice and human cells. Blunted production of H2S contributes to ovx-induced bone loss in mice by limiting the compensatory increase in bone formation elicited by ovx. Restoration of H2S levels is a potential novel therapeutic approach for postmenopausal osteoporosis. © 2015 American Society for Bone and Mineral Research. Source
Bianchi M.,Laboratorio NanoBiotecnologie NaBi |
Russo A.,Laboratorio NanoBiotecnologie NaBi |
Russo A.,Laboratorio Of Biomeccanica E Innovazione Tecnologica |
Lopomo N.,Laboratorio NanoBiotecnologie NaBi |
And 9 more authors.
Journal of Materials Chemistry B
Wear of ultra-high molecular weight polyethylene (UHMWPE) has been recognized as the main cause for long-term revision in joint arthroplasty. A new approach to overcome this detrimental issue is here presented: zirconia (ZrO2) thin films were directly deposited onto the surface of UHMWPE by Pulsed Plasma Deposition (PPD) technique. The obtained films were structurally, morphologically and mechanically characterized by X-ray diffraction, scanning electron microscopy and nanoindentation tests, respectively. The critical fracture load was estimated by the analysis of the indenter footprints, while the adhesion degree was evaluated by a cross-cut tape test. Zirconia films exhibited a fully cubic structure, with densely packed grains, whereas mechanical tests showed that hard, tough and well-adherent films were deposited. These preliminary results suggested the feasibility of pursuing this alternative route to improve UHMPWE performances while preserving its well-established mechanical properties. © 2013 The Royal Society of Chemistry. Source
Cetrullo S.,University of Bologna |
D'Adamo S.,University of Bologna |
Tantini B.,University of Bologna |
Borzi R.M.,Laboratorio Of Immunoreumatologia E Rigenerazione Tessutale |
And 2 more authors.
Critical Reviews in Eukaryotic Gene Expression
Cells adapt their metabolism and activities in response to signals from their surroundings, and this ability is essential for their survival in the face of environmental changes. In mammalian tissues a deficit of these mechanisms is commonly associated with cellular aging and degenerative diseases related to aging, such as cardiovascular disease, cancer, immune system decline, and neurological pathologies. Several proteins have been identified as able to respond directly to energy, nutrient, and growth factor levels and stress stimuli in order to mediate adaptations in the cell. Many of these proteins are enzymes that positively or negatively modulate the autophagic process. This review focuses on biochemical mechanisms involving enzymes—specifically, mTOR, AMPK, and Sirt1—that are currently considered important for these adaptive responses, providing an overview of the interactions of the main players in this process. © 2015 Begell House, Inc. Source
Torreggiani E.,University of Ferrara |
Lisignoli G.,Struttura Complessa Laboratorio Of Immunoreumatologia E Rigenerazione Tissutale |
Lisignoli G.,Laboratorio RAMSES |
Manferdini C.,Struttura Complessa Laboratorio Of Immunoreumatologia E Rigenerazione Tissutale |
And 12 more authors.
Journal of Cellular and Molecular Medicine
The pathways that control mesenchymal stem cells (MSCs) differentiation are not well understood, and although some of the involved transcription factors (TFs) have been characterized, the role of others remains unclear. We used human MSCs from tibial plateau (TP) trabecular bone, iliac crest (IC) bone marrow and Wharton's jelly (WJ) umbilical cord demonstrating a variability in their mineral matrix deposition, and in the expression levels of TFs including Runx2, Sox9, Sox5, Sox6, STAT1 and Slug, all involved in the control of osteochondroprogenitors differentiation program. Because we reasoned that the basal expression level of some TFs with crucial role in the control of MSC fate may be correlated with osteogenic potential, we considered the possibility to affect the hMSCs behaviour by using gene silencing approach without exposing cells to induction media. In this study we found that Slug-silenced cells changed in morphology, decreased in their migration ability, increased Sox9 and Sox5 and decreased Sox6 and STAT1 expression. On the contrary, the effect of Slug depletion on Runx2 was influenced by cell type. Interestingly, we demonstrated a direct in vivo regulatory action of Slug by chromatin immunoprecipitation, showing a specific recruitment of this TF in the promoter of Runx2 and Sox9 genes. As a whole, our findings have important potential implication on bone tissue engineering applications, reinforcing the concept that manipulation of specific TF expression levels may elucidate MSC biology and the molecular mechanisms, which promote osteogenic differentiation. © 2011 The Authors Journal of Cellular and Molecular Medicine © 2011 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd. Source
Gabusi E.,Laboratorio RAMSES |
Gabusi E.,Science Laboratorio Of Immunoreumatologia E Rigenerazione Tissutale |
Manferdini C.,Laboratorio RAMSES |
Manferdini C.,Science Laboratorio Of Immunoreumatologia E Rigenerazione Tissutale |
And 15 more authors.
Journal of Cellular Physiology
Fluctuation in extracellular calcium (Ca2+) concentration occurs during bone remodeling. Free ionized Ca2+ plays a critical role in regulating osteoblast functions. We analyzed the effects of different concentrations of free ionized Ca2+ (0.5, 1.3, and 2.6mM) on human osteoblasts and we evaluated osteoblastic phenotype (marker expression and cell morphology) and functions (osteogenic differentiation, cell proliferation, and cell signaling). Our data show human osteoblasts that chronically stimulated with 0.5, 1.3, or 2.6mM Ca2+ significantly increase intracellular content of alkaline phosphatase, collagen type I, osteocalcin, and bone sialoprotein, whereas collagen type XV was down-modulated and RUNX2 expression was not affected. We also found a Ca2+ concentration-dependent increase in osteogenic differentiation and cell proliferation, associated to an increase of signaling protein PLCβ1 and p-ERK. Human osteoblast morphology was affected by Ca2+ as seen by the presence of numerous nucleoli, cells in mitosis, cell junctions, and an increased number of vacuoles. In conclusion, our data show a clear phenotypical and functional effect of extracellular Ca2+ on human osteoblasts and support the hypothesis of a direct role of this cation in the bone remodeling processes. © 2011 Wiley Periodicals, Inc. Source