Characterization of skeletal alterations in a model of prematurely aging mice

Abstract

An age-related bone loss occurs, apparently associated with the concomitant increase in an oxidative stress situation. However, the underlying mechanisms of age-related osteopenia are ill defined since these studies are time consuming and require the use of many animals (mainly rodents). Here, we aimed to characterize for the first time the bone status of prematurely aging mice (PAM), which exhibit an increased oxidative stress. Tibiae from adult (6 months) PAM show an increase in bone mineral density (BMD) and bone mineral content (assessed by bone densitometry) versus those in their normal counterparts (non-prematurely aging mice, NPAM) and similarly decreased in both kinds of mouse with age. However, at this bone site, trabecular BMD (determined by μ-computerized tomography) was similar in both adult PAM and old (18 months) NPAM. Femurs from these groups of mice present an increase in oxidative stress, inflammation, osteoclastogenic, and adipogenic markers, but a decrease in the gene expression of osteoblastic differentiation markers and of the Wnt/β-catenin pathway. Our findings show that adult PAM recapitulate various age-related bone features, and thus are a suitable model for premature bone senescence studies.

Multipotential Stromal Cell Abundance in Cellular Bone Allograft: Comparison with Fresh Age-Matched Iliac Crest Bone and Bone Marrow Aspirate

“…To its advantage, Osteocel is obtained from younger donors with an average age of approximately 30 years [20]. Furthermore, gene expression of Osteocel samples demonstrated the high expression of BMPs 2 and 6 and the reduction in inhibitors such Gremlin-1 [52]; this is likely to enhance the graft’s osteoinductivity and be particularly beneficial for patients with co-morbidities such as diabetes [53]. The overall transcript profile of the Osteocel resembled that of osteoblasts and MSCs [36,38,54] rather than fibroblasts (Table 1).…”

Treatment with N- and C-Terminal Peptides of Parathyroid Hormone-Related Protein Partly Compensate the Skeletal Abnormalities in IGF-I Deficient Mice

“…Osteocytes were counted in 4 to 6 random x400-fields per sample in a cortical bone segment between the growth plate and the mid-diaphysis; the corresponding mean score value was normalized to the bone area of each sample. Osteoblasts, identified by their cuboidal shape and localization on bone surfaces and multinuclear osteoclasts (with 3 or more nuclei) [26] , [49] , were counted in a 0.8-mm 2 area of the tibial metaphysis immediately below the growth plate. Evaluations were performed by 2–3 independent observers in a blinded fashion for each mouse.…”

“…18S ribosomal RNA or the mouse ribosomal phosphoprotein P0 ( Rplp0 ) was used as endogenous control gene to normalize the expression data obtained. The relative quantification values (RQ) between Igf1 -null and wild type mice (treated or untreated) were determined by the 2 −ΔΔCt method, where ΔΔCt = ΔC target gene – ΔC reference gene [50] , and data were expressed as mRNA relative levels vs corresponding values in untreated wild type, as reported [38] , [49] .…”

“…Mouse intact tibiae from each experimental animal were homogenized in 50 mM Tris-HCl, pH 7.5, 150 mM NaCl, 2 mM EDTA, 2 mM EGTA, 0.2% Triton X-100, 0.3% NP-40, 1 mM dithiothreitol and protease and phosphatase inhibitor cocktail (Sigma-Aldrich) as described [49] . Protein concentration was measured by bicinchoninic acid-based assay (Thermo Fisher Scientific, Rockford, IL) using bovine serum albumin (BSA) as standard.…”

El estrés oxidativo como posible diana terapéutica en la osteoporosis asociada al envejecimiento

“…Although some researchers have raised questions about whether oxidative stress is a cause or consequence of aging, in recent years it has been implicated in the bone deterioration 49 . Using various animal models: premature aging, osteoporosis due to estrogen deficit (after ovariectomy) or diabetes, increased oxidative stress markers was found to decrease bone formation mechanisms [50][51][52][53][54] . The effects of oxidative stress to induce deleterious effects on bone tissue are not yet well known.…”