Correction of inherited skeletal abnormalities, traumas affecting wide bone areas and non-healing fractures require efficient bone formation and regeneration. Bone morphogenetic proteins (BMPs) are signa­ling molecules that play a crucial role in bone and cartilage formation and regeneration. Osteoinductive properties of existing hydroxyapatite-based osteoplastic materials are frequently insufficient for efficient bone regeneration, thus raising a requirement for novel matrices involving BMPs for highly efficient local induction of bone formation at the area of the bone defect. The aim of this study was conducting in vitro optimization of osteoinductive properties of recombinant BMPs preparations to be used in bone regenerative practice. Recombinant BMPs were produced in human embryonic kidney 293 cells upon their transfection or co-transfection with plasmids expressing BMP2 and BMP7 at different ratios. A quality of BMP preps was validated based on their ability to induce in vitro osteoblast differentiation of C2C12 cells. Alkaline phosphatase that is widely used as a marker of osteoblast differentiation was measured spectrophotometrically. We found that the most effective inducer of osteoblast differentiation was recombinant BMP preparation produced upon cotransfection of 85% of BMP2 and 15% of BMP7 plasmids, that is most likely due to generation of conditions most favorable for formation of BMP2/7 heterodimers. Frozen BMP2/7 preparations stored for 3 h in experimental setup and for several weeks in routine work do not lose their osteoinductive properties compared with freshly prepared BMP2/7 preparations and can be successfully used for generation of highly efficient bone regenerative matrices.

Rheumatoid arthritis (RA) is a severe autoimmune inflammatory disease leading to chronic pain in the

Rheumatoid arthritis (RA) is an autoimmune inflammatory disease of yet unknown etiology. Tumor necrosis factor α (TNFα are central players in the inhibition of activity of skeletogenesis. The aim of this study was to evaluate the anti-inflammatory activity of novel 4-thiazolidinone-based derivatives towards TNFα-induced pro-inflammatory effects during bone formation. We performed in vitro evaluation of functional effects of 4-thiazolidinones denoted as 0.1, 0.3 and 1.0 μM) on the TNFα-mediated inhibition of the BMP-induced osteoblast differentiation in mouse mesenchymal precursor (stem) cells of C2C12 line. Treatment of these cells with TNFα completely inhibited their myogenic differentiation, as well as strongly inhibited the BMP-induced osteogenesis. Strikingly, the treatment of C2C12 cells with

Rheumatoid arthritis (RA) is a chronic inflammatory disorder remodelling, in particular, during RA progression.