BackgroundNon-steroidal anti-inflammatory drugs (NSAIDs) are frequently prescribed to relieve pain and inflammation. These NSAIDs have also analgesic effects and can be administered via oral, injectable, and topical routes. During inflammation, a number of synovial mediators and cytokines are released which decrease the pH level of the synovial fluid. Administration of acidic NSAIDs further decreases the pH levels and hence contributes to the destruction of the cartilage. To our knowledge, no cellular-based study regarding the chondrotoxicity of phenyl alkanoic acid derivatives on NSAIDs was conducted before. Thus, the aim of this pioneering study was to examine the effect of frequently prescribed NSAIDs, a phenyl alkanoic acid derivative, flurbiprofen, on the proliferation and differentiation of human primer chondrocyte cultures in vitro.MethodsPrimer chondrocyte cultures were prepared from osteochondral tissue obtained during surgery for gonarthrosis. Samples not exposed to the pharmacological agent were used as the control group. The samples were treated with 1, 10, 100, 250, 500, or 1000 μM of the agent for 24, 48, and 72 h. The cell viability, toxicity, and proliferation were assessed with MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) analysis and prechondrocytic precursor stage-specific embryonic antigen-1 (SSEA-1) expression using a commercial ELISA kit spectrophotometrically. The surface morphology of the samples in each group was compared using an inverted light microscope and an environmental scanning electron microscope (ESEM). An analysis of variance was used to compare between-group differences. Tukey’s honest significant difference (HSD) method (95 % confidence interval) was used to evaluate the differences and significance in averages. The alpha significance value was considered <0.01.ResultsStatistically significant cytotoxicity was observed in the treatment groups. NSAID had a significant negative effect on the proliferation and differentiation of chondrocytes as compared to the control group (p < 0.01).ConclusionBefore administering phenyl alkanoic acid derivatives in the clinical setting, their role in suppressing the proliferation and differentiation of chondrocytes should be taken into account. Thus, caution should be given when prescribing these drugs.

Purpose: Methylphenidate (MPH) derivative drugs are used because of psychostimulants effects on attention-deficit hyperactivity disorder in children and adults. As far as we know, toxic or anti-proliferative effects of MPH against cartilage tissue were not studied in the literature. The present study was carried out to investigate the possible effects of MPH on the proliferation, viability and differentiation of primary human chondrocytes, in vitro. Methods: Monolayer primary chondrocyte cultures were prepared using osteochondral tissue obtained from patients who underwent a total knee prosthesis operation. Stock solution of MPH was prepared and aliquots having 1–1000 µM concentrations of the drug was composed. These solutions were applied to the wells containing cultured chondrocyte samples within the well plates. Control groups were composed of pure chondrocyte culture and no solution was added into them. All groups were evaluated at 24, 48 and 72 h in order to determine the possible negative effects of the drug on the chondrocytes. The data were evaluated by Tukey’s honestly significantly different test following analysis of variance. Results: In the group where MPH was applied, it was found that viability, proliferation and stage-specific embryonic antigen-1 protein expression were decreased in comparison to the control group. Conclusions: It was emphasized that clinicians should not disregard the fact that this drug might suppress chondrocyte cell proliferation and chondrogenic differentiation.

Non-steroidal anti-inflammatory drugs (NSAIDs) that are applied through oral, injectable or topical routes have been widely used in painful and inflammatory musculoskeletal diseases. The current study aimed to determine whether naproxen, an aryl acetic acid derivative with analgesic and anti-inflammatory effects, has a toxic effect on human chondrocytes. Samples containing monolayer primary chondrocyte cultures were prepared following resection from osteochondral tissues obtained from patients with gonarthrosis. Cell viability, toxicity and proliferation and levels of stage-specific embryonic antigen-1, a precursor to human prechondrocytes, were evaluated spectrophotometrically. The results from the untreated control group were compared with those of the study groups, where naproxen was administered in varying doses (1–1,000 µM). Surface morphologies of the cells were compared using inverted light and environmental scanning electron microscopy. Treatment groups were compared by analysis of variance with Tukey's honest difference post hoc test. P<0.01 was considered to indicate a statistically significant difference. The research revealed significant changes to proliferation and differentiation of chondrocytes in all treatment groups (P<0.01). Naproxen was demonstrated to suppress chondrocyte proliferation and differentiation, which may be an important factor to consider when prescribing this medication to patients.

Background Use of biodegradable and biocompatible materials in the orthopedic surgery is gaining popularity. In this research, the rate of controlled release of a bilayered prototype biomaterial designed to promote osteoblastic and tenoblastic activity was calculated using pharmacochemical methods. Methods The first part of the design, composed of a sodium tetraborate, polyvinyl alcohol, and starch based hydrogel, was loaded with bone morphogenic protein-2. The second part which was composed of a sodium tetraborate, polyvinyl alcohol, and chitosan based hydrogel was loaded with bone morphogenic protein-12. Osteochondral and tendon tissue specimens were obtained from patients with a diagnosis of gonarthrosis and primary bone cells and tendon cells cultures were prepared following treatment with collagenase enzyme. Cell samples were collected from the groups by means of an invert light microscope and environmental scanning electron microscope underwent at the 1st and 21st days. The level of osteogenic differentiation was measured by the activity of alkaline phosphatase. For the statistical evaluation of the obtained data, groups were compared with post hoc Tukey test following analysis of variance. Level of significance was accepted to be <0,01. Results Both osteogenic and tenogenic stimulation were observed in the cultured specimens. In comparison to the control groups, the rate of proliferation of healthy cells was found to be higher in the groups to which the design was added (p < 0.01). Conclusions Our research is a preliminary report that describes a study conducted in an in vitro experimental setting. We believe that such prototype systems may be pioneers in targeted drug therapies after reconstructional surgeries.

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