ABSTRACT
Estrogen deficiency promotes bone loss and skeletal muscle dysfunction. Peroxisome proliferator-activated receptors (PPARs) have 3 subtypes (α, δ, and γ). PPARγ agonists induce bone loss, whereas PPARα agonists increase bone mass. Although PPARδ agonists are known to influence skeletal muscle metabolism, the skeletal effects are unsettled. This study investigated the musculoskeletal effects of the PPARδ agonist GW501516 in ovariectomized (OVX) rats. Female Sprague Dawley rats, 12 weeks of age, were allocated to a sham-operated group and 3 OVX groups; high-dose GW501516 (OVX-GW5), low-dose GW501516 (OVX-GW1), and a control group (OVX-CTR), respectively (n = 12 per group). Animals received GW501516 or vehicle (methylcellulose) daily for 4 months by gavage. Bone mineral density (BMD) was assessed by dual x-ray absorptiometry at the femur, spine, and whole body. Bone microarchitecture at the proximal tibia was assessed by microcomputed tomography, and dynamic histomorphometry was performed. Quadriceps muscle morphology and the relative expression of mitochondrial proteins were analyzed. Bone metabolism markers and metabolic markers were measured in plasma. After 4 months, the OVX-GW5 group displayed lower femoral BMD than OVX-CTR. Trabecular separation was higher in the GW-treated groups, compared with OVX-CTR. The OVX-GW5 group also exhibited lower cortical area fraction and a higher structure model index than OVX-CTR. These effects coincided with impaired bone formation in both GW groups. The OVX-GW5 group displayed elevated triglyceride levels and reduced adiponectin levels, whereas no effects on muscle morphology or mitochondrial gene expression appeared. In summary, the PPARδ agonist GW501516 negatively affected bone properties in OVX rats, whereas no effects were detected in skeletal muscle.
Subject(s)
Muscle, Skeletal/drug effects , Osteoblasts/drug effects , PPAR delta/agonists , Thiazoles/pharmacology , Tibia/drug effects , Absorptiometry, Photon , Animals , Body Composition/drug effects , Cell Differentiation/drug effects , Cell Line , Cell Proliferation/drug effects , Female , Immunoassay , Rats , Rats, Sprague-Dawley , Real-Time Polymerase Chain ReactionABSTRACT
The aim of this study was to investigate the effect of TiO2 scaffold (SC) coated with an alginate hydrogel containing a proline-rich peptide (P2) on osteoblast proliferation and differentiation in vitro. Peptide release was evaluated and a burst release was observed during the first hours of incubation, and then progressively released overtime. No changes were observed in the cytotoxicity after 48 h of seeding MC3T3-E1 cells on the coated and uncoated TiO2 SC. The amount of cells after 7 days was higher on uncoated TiO2 SC than on alginate-coated TiO2 SC, measured by DNA content and scanning electron microscope imaging. In addition, while lower expression of integrin beta1 was detected for alginate-coated TiO2 SC at this time point, similar gene expression was observed for other integrins, fibronectin-1, and several osteoblast differentiation markers. After 21 days, gene expression of integrin beta3, fibronectin-1, osterix, and collagen-I was increased in alginate-coated compared to TiO2 SC. Moreover, increased gene expression of integrin alpha8, bone morphogenetic protein 2, interleukin-6, and collagen-I was found on P2 alginate-coated TiO2 SC compared to alginate-coated TiO2 SC. In conclusion, our results indicate that alginate-coated TiO2 SC can act as a matrix for delivery of proline-rich peptides increasing osteoblast differentiation. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2013.
Subject(s)
Alginates/pharmacology , Coated Materials, Biocompatible/pharmacology , Hydrogel, Polyethylene Glycol Dimethacrylate/pharmacology , Osteoblasts/cytology , Peptides/pharmacology , Tissue Scaffolds/chemistry , Titanium/pharmacology , Amino Acid Sequence , Animals , Biomarkers/metabolism , Cell Adhesion/drug effects , Cell Adhesion/genetics , Cell Count , Cell Differentiation/drug effects , Cell Line , Cell Proliferation/drug effects , Culture Media , Gene Expression Regulation/drug effects , Glucuronic Acid/pharmacology , Hexuronic Acids/pharmacology , L-Lactate Dehydrogenase/metabolism , Mice , Molecular Sequence Data , Osteoblasts/drug effects , Osteoblasts/metabolism , Peptides/chemistry , Proline-Rich Protein Domains , RNA, Messenger/genetics , RNA, Messenger/metabolismABSTRACT
Tuberculosis morbidity has been markedly reduced in the Esthonian SSR. In children and yough tuberculosis is no more a problem. Among the new cases of adults formerly diseases or with inactive lesions in the lungs amount to 44,5% of the incidence. In the Esthonian SSR all persons with any lesions in the lungs are registered in an individual record index. They all are now supervised in intervals of a year and less. Another aggravating conditions exist in 13,6% of these persons. Chemotherapy or chemoprophylaxis is done in this group. A marked reduction of morbidity has been attained in this way.
