Cartilage Chondrocyte Apoptosis Research Articles

Jintiange Capsules Ameliorate Osteoarthritis by Modulating Subchondral Bone Remodeling and Protecting Cartilage Against Degradation.

Osteoarthritis (OA) is the most prevalent joint disease worldwide, making it a major cause of pain and disability. Identified as a chronic and progressive disease, effective treatment at the early stages of OA has become critical to its management. Jintiange (Jtg) capsules are a traditional Chinese medicine produced from multiple organic components of various animal bones and routinely used to treat osteoporosis in China. However, the effect of Jtg on subchondral bone and cartilage degeneration in OA remains unknown. The purpose of the present study was to investigate the biomolecular role and underlying mechanisms of Jtg in OA progression. Herein, we found that Jtg inhibited receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast formation and it functions through the NF-κB signaling pathway. Jtg also inhibited chondrocyte apoptosis via reducing the reactive oxygen species concentration in these cells. Moreover, in vivo evaluation revealed that Jtg significantly attenuates subchondral bone remodeling and cartilage destruction in anterior cruciate ligament transection (ACLT) mouse models. Taken together, our data demonstrate that Jtg inhibits osteoclast differentiation in subchondral bone and chondrocyte apoptosis in cartilage, supporting its potential therapeutic value for treating OA.

Effects of Streptococcus thermophilus on anterior cruciate ligament transection-induced early osteoarthritis in rats.

Osteoarthritis (OA) is the most common joint disorder and is classically defined as a progressively degenerative disease of articular cartilage. It manifests as joint pain and disability and currently has no comprehensive treatments. The primary purpose of the present study was to test the effects of probiotics, Streptococcus thermophilus (TCI633), on anterior cruciate ligament transection (ACLT)-induced experimental osteoarthritis (OA) in rats. In the current study, the experimental groups were given TCI633 (5x109, 5x1010 and 5x1011 CFU/kg/day) and glucosamine sulfate (250 mg/kg) between week 8 and 20 following ACLT. The results showed that oral administration of TCI633 and glucosamine had significant therapeutic effects on pain behaviors and knee swelling. Dose-dependent effects of TCI633 were also observed in ACLT-treated rats. Histopathological analysis demonstrated that ACLT+TCI633 (5x109, 5x1010 and 5x1011 CFU/kg/day) improved the synovial inflammation and cartilage damage of ACLT rats. Histology evaluation using the Osteoarthritis Research Society International system and synovial inflammatory score analysis showed the dose-dependent inhibition of TCI633 on synovial inflammation and cartilage damage. Immunohistochemical staining and TUNEL apoptosis staining showed that TCI633 could effectively increase the expression of type II collagen and reduce the amount of chondrocyte apoptosis in cartilage. Therefore, the present study demonstrated that oral intake of TCI633 could significantly suppressing pain behavior, reduce joint swelling and synovial tissue inflammation and increase type II collagen expression in cartilage. There was also a reduction in chondrocyte apoptosis and decreased progression of OA in ACLT-treated rats.

Parathyroid hormone (1-34) ameliorates cartilage degeneration and subchondral bone deterioration in collagenase-induced osteoarthritis model in mice.

AimsParathyroid hormone (PTH) (1-34) exhibits potential in preventing degeneration in both cartilage and subchondral bone in osteoarthritis (OA) development. We assessed the effects of PTH (1-34) at different concentrations on bone and cartilage metabolism in a collagenase-induced mouse model of OA and examined whether PTH (1-34) affects the JAK2/STAT3 signalling pathway in this process.MethodsCollagenase-induced OA was established in C57Bl/6 mice. Therapy with PTH (1-34) (10 μg/kg/day or 40 μg/kg/day) was initiated immediately after surgery and continued for six weeks. Cartilage pathology was evaluated by gross visual, histology, and immunohistochemical assessments. Cell apoptosis was analyzed by TUNEL staining. Microcomputed tomography (micro-CT) was used to evaluate the bone mass and the microarchitecture in subchondral bone.ResultsEnhanced matrix catabolism, increased apoptosis of chondrocytes in cartilage, and overexpressed JAK2/STAT3 and p-JAK2/p-STAT3 were observed in cartilage in this model. All of these changes were prevented by PTH (1-34) treatment, with no significant difference between the low-dose and high-dose groups. Micro-CT analysis indicated that bone mineral density (BMD), bone volume/trabecular volume (BV/TV), and trabecular thickness (Tb.Th) levels were significantly lower in the OA group than those in the Sham, PTH 10 μg, and PTH 40 μg groups, but these parameters were significantly higher in the PTH 40 μg group than in the PTH 10 μg group.ConclusionIntermittent administration of PTH (1-34) exhibits protective effects on both cartilage and subchondral bone in a dose-dependent manner on the latter in a collagenase-induced OA mouse model, which may be involved in regulating the JAK2/STAT3 signalling pathway.Cite this article: Bone Joint Res 2020;9(10):675–688.

Protective Effect of Alendronate on Lumbar Facet Degeneration in Ovariectomized Rats.

BackgroundFacet joint degeneration (FJD) is a potential source of lower back pain, and estrogen deficiency can accelerate FJD. The present study aimed to investigate the effects of alendronate (ALN) on FJD induced by ovariectomy (OVX) in rats.Material/MethodsThirty female Sprague-Dawley rats underwent either bilateral OVX (n=20) or sham surgery (n=10). The OVX rats subsequently received either subcutaneous ALN (70 μg/kg/week) or vehicle for 12 weeks. Subchondral bone mass and microarchitecture were evaluated by micro-computed tomography. Cartilage degradation was evaluated by toluidine blue staining and histological scoring.ResultsCompared with the Sham group, the OVX group had significantly decreased bone mineral density, bone volume/trabecular volume, and trabecular thickness, significantly increased trabecular separation in subchondral bone, and significantly higher histological score for cartilage degeneration, particularly loss of cartilage thickness. ALN treatment significantly reversed the changes in subchondral bone, preserved cartilage thickness, and reduced the histological score. Immunohistochemical analyses showed significantly decreased expression of ADAMTS-4, MMP-13, and caspase-3 in the OVX+ALN group compared with the OVX group.ConclusionsTreatment with ALN suppressed bone loss, subchondral bone architecture deterioration, and cartilage degeneration in OVX rats, which can be explained by roles of ALN in preservation of subchondral bone mass and microarchitecture, and counteraction of catabolism and chondrocyte apoptosis in cartilage.

The expression of p-ATF2 involved in the chondeocytes apoptosis of an endemic osteoarthritis, Kashin-Beck disease

BackgroundThe purpose of the study was to understand the function and expression of ATF2 by JNK and p38 signal pathways in the chondrocytes apoptosis of articular cartilage of the Kashin-Beck disease (KBD).MethodsThe changes of ATF2, JNK and p38 mRNAs and proteins were investigated between cartilage and chondrocyte as well as KBD and normal. JNK and p38 inhibitors were used as treatments to prevent apoptosis in chondrocytes from KBD patients.ResultsIt was found that the protein levels of p-p38, p-JNK, ATF2 and p-ATF2 increased in KBD human cartilage which is in line with the higher mRNA levels of p38, JNK and ATF2 as compared both with normal cartilage and KBD chondrocytes. In addition, p-ATF2 was only detected in KBD cartilage. Furthermore, JNK inhibitor was more effective than p38 inhibitor in preventing chondrocyte apoptosis at equal concentrations of 10 μM.ConclusionThese findings indicated the expression of p-ATF2 by JNK and p38 signal pathways involved in the chondrocyte apoptosis in cartilage with KBD.