Skeletal Effects of a Prolonged Oral Metformin Treatment in Adult Wistar Rats.

INTRODUCTION: We previously showed that a 3-week oral metformin (MET) treatment enhances the osteogenic potential of bone marrow stromal cells (BMSCs) and improves several bone histomorphometric parameters in Wistar rats with metabolic syndrome (MetS). However, the skeletal effects of extended periods of MET need to be completely elucidated. Hence, in this study, the impact of a prolonged (3-month) MET treatment was investigated on bone architecture, histomorphometric and biomechanics variables, and osteogenic potential of BMSCs in Wistar rats with or without MetS. MATERIALS AND METHODS: Young male Wistar rats (n=36) were randomized into four groups (n=9) that received either 20% fructose (F), MET (MET), F plus MET treatments (FMET), or drinking water alone (Veh). Rats were euthanized, blood was collected, and bones were dissected and processed for peripheral quantitative computed tomography (pQCT) analysis, static and dynamic histomorphometry, and bone biomechanics. In addition, BMSCs were isolated to determine their osteogenic potential. RESULTS: MET affected trabecular and cortical bone, altering bone architecture and biomechanics. Furthermore, MET increased the pro-resorptive profile of BMSCs. In addition, fructose-induced MetS practically did not affect the the structural or mechanical variables of the skeleton. CONCLUSION: A 3-month treatment with MET (with or without MetS) affects bone architecture and biomechanical variables in Wistar rats.

Vanadium(IV) complexes inhibit adhesion, migration and colony formation of UMR106 osteosarcoma cells.

Vanadium is a trace element widely distributed in the environment. In vertebrates it is mainly stored in bone tissue. The unique cellular environment in the bone and the variety of interactions that mediate cancer metastasis determine that certain types of cancer, such as breast and prostate cancer, preferentially metastize in the skeleton. Since this effect usually signifies serious morbidity and grave prognosis there is an increasing interest in the development of new treatments for this pathology. The present work shows that vanadium complexes can inhibit some parameters related to cancer metastasis such as cell adhesion, migration and clonogenicity. We have also investigated the role of protein kinase A in these processes.

Antitumoral properties of two new vanadyl(IV) complexes in osteoblasts in culture: role of apoptosis and oxidative stress.

BACKGROUND: Vanadium derivatives have been reported to display different biological effects, and in particular antineoplastic activity has been demonstrated in both in vivo and in vitro studies. PURPOSE. To study the effect of two new organic vanadyl(IV) complexes (one with glucose, GluVO, and the other with naproxen, NapVO) in osteosarcoma cells. METHODS: UMR106 osteosarcoma cells and, for comparison, nontransformed MC3T3E1 osteoblasts were used. Proliferation and differentiation were assessed using the crystal violet assay and ALP specific activity, respectively. Morphological alterations were assessed by light microscopy. Lipid peroxidation was evaluated in terms of production of thiobarbituric acid-reactive substances (TBARS) and apoptosis was measured using annexin V. Extracellular regulated kinase (Erk) activation was investigated by Western blotting. RESULTS: Vanadium complexes caused morphological alterations and they strongly inhibited UMR106 cell proliferation and differentiation. In contrast, in MC3T3E1 cells, these vanadium derivatives had a relatively weak action. In UMR106 tumoral cells there was a significant increase in TBARS production. Both vanadium complexes induced apoptosis and activation of Erk. PD98059, an inhibitor of Erk phosphorylation, did not block the vanadium-induced antitumoral action. However, the antioxidants vitamins C and E abrogated the apoptosis and TBARS production induced by the vanadium complexes. CONCLUSIONS: GluVO and NapVO exerted an antitumoral effect in UM106 osteosarcoma cells. They inhibited cell proliferation and differentiation. While the Erk cascade seems not to be directly related to the bioactivity of these vanadium derivatives, the action of both vanadium complexes with organic ligands may be mediated by apoptosis and oxidative stress.