[Experimental study on the regulation of subchondral bone plate osteoprotegerin/receptor activator of nuclear factor kappa-B ligand system by berberine to retard the development of osteoarthritis in rabbits].

OBJECTIVE: To investigate the effect of intra-articular berberine injection on the structural remodeling of subchondral bone plate and osteoprotegerin/receptor activator of nuclear factor kappa-B ligand(OPG/RANKL) system expression in rabbits with osteoarthritis(OA). METHODS: Forty 12-month-old male rabbits with an average of(2.73±0.18) kg of body weight, underwent left anterior cruciate ligament transection(ACLT), and were divided into berberine group and placebo groups after operation, 20 rabbits in each group. The berberine group received intra-articular injection of 100 µmol/L berberine 0.3 ml every week for 6 weeks. In placebo group, the same dose of 0.9% sodium chloride injection was injected into the left knee joint cavity every week for 6 weeks. Another 20 12-month-old male rabbits, weighing (2.68±0.18) kg, underwent sham operation on the left knee joint without intra-articular injection intervention (sham operation group). On the last day of the sixth week after operation, three groups of animals were sacrificed to obtain knee joint specimens. The femoral medial condyle samples were obtained for histological evaluation of cartilage and subchondral bone, Mankin scoring system was used to evaluate articular cartilage structure. Image-Pro Plus(IPP) software was used to evaluate subchondral bone plate bone volume(BV), bone volume/total volume(BV/TV), trabecular circumference(TC), mean trabecular thickness (Tb.Th). Real-time quantitative reverse transcription polymerization Enzyme chain reaction(reverse transcription-polymerase chain reaction, RT-PCR) was used to detect the mRNA expression levels of OPG and RANKL in subchondral bone tissue at 6 weeks after operation. RESULTS: The cartilage structure evaluation showed that the surface of cartilage tissue in the sham operation group was smooth and flat, and the safranin coloration was full in the full thickness of the cartilage;the cartilage tissue in the berberine group showed uneven surface layer, and the staining of safranin O was mildly decreased;the surface layer fibrosis was seen in placebo group, Safranin O faded significantly. The Mankin score in the berberine group was lower than that in placebo group(P<0.01), but higher than that in sham operation group(P<0.01). The structural evaluation of subchondral bone plate showed that the trabecular bone in sham-operated group was densely arranged;after berberine intervention, the trabeculae were closely arranged;the subchondral bone trabeculae in placebo group were relatively sparse, and the distance between trabeculae was wider. Subchondral bone plate IPP software evaluation showed that BV, BV/TV, TC, Tb.Th in berberine group were higher than those in placebo group(P<0.01), BV, BV/TV, TC, Tb.Th in berberine group were higher than those in placebo group(P<0.01), while lower than the sham operation group (P<0.01). PCR test results showed that the expression of OPG mRNA in the berberine group was significantly higher than that in placebo group(P<0.01), and OPG mRNA in the berberine group was lower than that in sham operation group (P<0.01). There was no significant difference in mRNA expression of RANKL among three groups(P>0.05);the ratio of OPG/RANKL in berberine group was higher than that in placebo group(P<0.01), but lower than that in sham operation group(P<0.01). CONCLUSION: Intra-articular injection of berberine can effectively inhibit the resorption of subchondral bone in the early stage of OA and delay the development of the disease. The specific mechanism may be that berberine maintains the balance of OPG/RANKL system by up-regulating the expression of OPG gene in subchondral bone.

Dehydroepiandrosterone and age-related musculoskeletal diseases: Connections and therapeutic implications.

Musculoskeletal disorders related to ageing are one of the most common causes of mortality and morbidity among elderly individuals worldwide. The typical constitutive components of the musculoskeletal system, including bone, muscle, and joints, gradually undergo a process of tissue loss and degeneration as a result of life-long mechanical and biological stress, ultimately leading to the onset of a series of age-related musculoskeletal diseases, including osteoporosis (OP), sarcopenia, and osteoarthritis (OA). Dehydroepiandrosterone (DHEA), a precursor of androgen secreted mainly by the adrenal gland, has attracted much attention as a marker for senescence due to its unique age-related changes. This pre-hormone has been publicly regarded as an "antidote for ageing" because of its favourable effect against a wide range of age-related diseases, such as Alzheimer disease, cardiovascular diseases, immunosenescence and skin senescence, though its effect on age-related musculoskeletal diseases has been explored to a lesser extent. In the present review, we summarized the action of DHEA against OP, sarcopenia and OA. Extensive detailed descriptions of the pathogenesis of each of these musculoskeletal disorders are beyond the scope of this review; instead, we aim to highlight the association of changes in DHEA with the processes of OP, sarcopenia and OA. A special focus will also be placed on the overlapping pathogeneses among these three diseases, and the molecular mechanisms underlying the action of DHEA against these diseases are discussed or postulated.

Comparison between two rabbit models of posttraumatic osteoarthritis: A longitudinal tear in the medial meniscus and anterior cruciate ligament transection.

Animal osteoarthritis (OA) models have been developed to understand OA progression and evaluate new OA therapies. However, individual variations in joint lesions remain a critical problem in most current OA models. We established a novel rabbit model by creating a longitudinal tear in the medial meniscus body that was reproducible and similar to posttraumatic biomechanical disturbances in human OA. New Zealand rabbits underwent surgery and were assessed for 9 weeks. The rabbits were randomized into the sham control, medial meniscal tear (MMT), and anterior cruciate ligament transection (ACLT) groups. The animals were sacrificed at 4, 6, and 9 weeks posttreatment. The knee joints were harvested for histological and gene expression assessments. Both the MMT and ACLT procedures led to time-dependent degenerative changes in the femoral condyle cartilage. At each time point, the MMT group cartilage showed more severe degenerative changes than did the ACLT group cartilage. Consistently, inflammatory cytokine and catabolic gene expression were significantly higher, and anabolic gene expression was significantly lower in the MMT group than in the ACLT group. MMT treatment caused more severe structural damage to the cartilage and higher catabolic gene expression levels than the ACLT model at each time point. The MMT model may be highly beneficial in investigating posttraumatic OA (PTOA) development, especially PTOA from a meniscal injury. The MMT model replicated key features of human PTOA, including meniscal lesions, inflammatory responses, and the progression to osteoarthritic cartilage degeneration, thereby providing an exciting new avenue for translating promising treatments to clinical practice.

Effect of sintering temperature on mineral composition and heavy metals mobility in tailings bricks.

In this study, the mixing mechanism and phase transition process of different metals during the sintering of tailings bricks with four different metal oxides (CuO, PbO, ZnO, and CdO) at temperatures ranging from 700 to 1100 °C for 2 h were investigated. The properties of the sintered product was characterized and analyzed, and the results showed that the main crystalline phases are quartz, cristobalite, hematite, and mullite while the metal oxides are ascribed to copper ferrite spinel (CuFe2O4), gahnite (ZnAl2O4), zinc ferrite spinel (ZnFe2O4), lead feldspar (PbAl2Si2O8), and cadmium feldspar (CdAl2Si2O8). Further analysis indicates that the heavy metals were transited into spinel or silicate structures with favorable efficiency. This indicates a good heavy-metal fixation effect from the structural change after the sintering process. Finally, the leaching experiments of the sintered samples suggest that the metal leaching decreased to a low and stable value when the sintering temperature was higher than 950 °C, which meets the China standard (GB 5085.3-2007). The above results indicate that the sintering process facilitates the combination of Cu, Zn, Pb and Cd offering an effective and safe method for the application of materials that contain tailings.

Potential of dehydroepiandrosterone in modulating osteoarthritis-related pain.

Osteoarthritis (OA) is the most common form of degenerative arthropathy, and the primary symptom is chronic joint pain. Dehydroepiandrosterone (DHEA) exerts a chondroprotective effect against OA and has been reported to have potent structure-modifying effects on osteoarthritic cartilage, thereby attenuating disease progression. However, the ability of DHEA to modulate OA-related pain has not yet been verified. Recent evidence suggests that there may be a link between the pharmacological effects of DHEA and pain generation. For example, DHEA synthesized in the adrenal gland interferes directly with nerve growth factor (NGF) receptors, a major biochemical contributor to peripheral hypersensitivity. Similarly, endogenous DHEA produced in the spinal cord exerts a regulatory effect on nociception in neuropathic rats. In this short review, we discuss recent studies concerning crucial signalling cascades and molecular mechanisms involved in pain generation as well as the potential link between DHEA activity and nociception. Particular attention is given to the putative molecular mechanisms underlying the favourable efficacy of DHEA against pain generation. Elucidating the molecular mechanisms of DHEA against osteoarthritic pain may pave the way for the discovery and development of novel anti-OA drugs, as effective drugs for OA treatment are not currently available.

Toxicity evaluation of textile dyeing effluent and its possible relationship with chemical oxygen demand.

Textile dyeing wastewater was the focus of much research because of its adverse effect on aquatic biota. In the present research, textile dyeing influent and effluent samples were collected from four textile dyeing wastewater treatment plants (TDPs) in Guangdong province, China, and their conventional indicators and toxicity were examined to reveal relationships. The relationship between toxicity and chemical oxygen demand (COD) was clearly established at individual TDPs. Results indicated the highest removal efficiencies of 94.4%, 90.6%, 91.9%, 94.6%, 92.8% and 97.5% for TOC, mixed-liquor volatile suspended solids (MLVSS), COD, ammonia nitrogen (NH3-N), total phosphorus (TP) and colour, respectively. The primary clarifier used in TDP3 and TDP4 was beneficial for removing macromolecular organic substances, and membrane filtration and sedimentation basin employed at TDP1 and TDP2, respectively, helped to remove toxic substances. Toxicity to V. fischeri or D. subspicatus was found to be related to certain conventional indicators such as TOC, COD, TP, colour, and MLVSS, and was positively correlated with COD in different textile dyeing effluents (R2 > 0.84). It was recommended that the relationship between toxicity and COD in wastewater should be established individually at each plant. Therefore, this study could be useful in providing suggestions for guiding effluent management when no toxicity experiments were conducted.

Elimination and ecotoxicity evaluation of phthalic acid esters from textile-dyeing wastewater.

Phthalic acid esters (PAEs), presented in fabrics, surfactants and detergents, were discharged into the ecosystem during textile-dyeing wastewater treatment and might have adverse effects on water ecosystems. In this study, comprehensive investigations of the content and component distributions of 12 PAEs across different units of four textile-dyeing wastewater plants were carried out in Guangdong Province, China. Ecotoxicity assessments were also conducted based on risk quotients (RQs). On average, 93.54% TOC and 80.14% CODCr were removed following treatment at the four plants. The average concentration of Σ12PAEs in effluent was 11.78 µg/L. PAEs with highest concentrations were dimethylphthalate (6.58 µg/L), bis(2-ethylhexyl)phthalate (2.23 µg/L), and dibutylphthalate (1.98 µg/L). The concentrations of the main toxic PAEs were 2.23 µg/L (bis(2-ethylhexyl)phthalate), 0.19 µg/L (diisononylphthalate) and 0.67 µg/L (dinoctylphthalate); corresponding RQs were 1.4, 0.55, and 0.54 for green algae, respectively. The RQs of Σ12PAEs in effluent of the four plants were >0.1, indicating that Σ12PAEs posed medium or higher ecological risk to fish, Daphnia and green algae. Physicochemical-biochemical system was found to be more effective than biochemical-physicochemical system for TOC and CODCr removal, because pre-physicochemical treatment helped to remove macromolecular organic substances, and reduced the competition with other pollutants during biochemical treatment. However, biochemical-physicochemical system was more effective than physicochemical-biochemical system for elimination of PAEs and for detoxification, since the biochemical treatment might produce the toxic PAEs that could helpfully be settled by post-physicochemical treatment. Moreover, ecotoxicity evaluation was recommended for current textile-dyeing wastewater treatment plants.