Abstract: Objective To investigate the mechanism of cartilage injury and inflammation in the WHBE rabbit KOA model and the effect of platelet-rich fibrin releasates (PRFr) treatment on the KOA process, we established a WHBE rabbit KOA model by excision of medial collateral and partial patellar ligaments and administered a PRFr solution. Methods Twenty-four WHBE rabbits were randomly divided into three groups: normal control ( NC) group ( n= 6),model(KOA) group(n= 12), and cure(PRFr) group ( n= 6). KOA and PRFr groups were injected with 0. 5 mL saline and PRFr into both joint cavities on 7 and 14 postoperative days, respectively. At 4 and 8 weeks of modeling, the knee joint grade scoring, X-ray imaging, and gross scoring were performed. Serum levels of IL-1β, TNF-α, and MMP-13 were measured by ELISA. At 4 weeks, 6 animals in the KOA group were euthanized, and at 8 weeks, the remaining animals in each group were euthanized. Pathological sections were prepared after decalcification, and then HE, toluidine blue, and safranin O-fast green staining and immunohistochemical analysis of TGF-β, BMP3, and NF-κB were conducted. Results The Lequesne MG behavioral score, Mankin’ s score, and Pelletier score of WHBE rabbits after the operation were significantly increased compared with the NC group (P<0. 01). Pathological observations revealed surface defects of the cartilage and partial loss of chondrocytes. These result indicated that the KOA model was established successfully. In KOA rabbits, knee joint swelling, joint pain stimulation, and movement limitation were obvious. X-rays showed a high-density soft tissue shadow, indicating more joint effusion and a rough articular surface in general. After PRFr treatment, the serum levels of proinflammatory factors IL-1β, TNF-α, and MMP-13 in KOA model rabbits were significantly reversed (P<0. 05,P<0. 01). Additionally, the cartilage surface became smooth, and most chondrocytes were neatly distributed. Expression levels of TGF-β, BMP3, and NF-κB induced by KOA were also significantly decreased (P<0. 01). Conclusions We successfully established a KOA model in WHBE rabbits, and PRFr improved the cartilage injury and inflammation of the WHBE rabbit KOA model through TGF-β/ BMP and NF-κB pathways.

Abstract:MiR-138-5p is a microRNA that plays an important regulatory role in the pathogenesis of osteoarthritis.MiR-138-5p regulates various biological processes, including inflammation, cell apoptosis and proliferation, and matrix degradation in osteoarthritis, by modulating signaling pathways including nuclear factor-κB, Wnt / β-catenin, and phosphoinositide 3-kinase / AKT. This review summarizes the research progress regarding the mechanism of miR-138-5p in osteoarthritis.

Abstract:Osteoarthritis (OA) is a chronic degenerative disease with a high incidence rate among middle-aged and elderly people. It can cause joint pain, deformity, and functional impairment, leading to a heavy burden on patients and their families. Peroxisome proliferator-activated receptor γ (PPARγ) is a recently discovered ligand-dependent transcriptional regulatory factor that can regulate fat and carbohydrate metabolism, inflammation, and immune processes. Research has shown that the PPARγ gene plays an important role in OA cartilage degeneration, synovitis inflammation, and adipose lesions, and can affect OA progression through signaling pathways such as the AMP-activated protein kinase, Wnt, and sirtuin 1 pathways. This review focuses on the role and mechanism of the PPARγ gene in OA, in relation to jointrelated tissues and key signaling pathways.

Abstract: Objective 　To explore the effect of Rehmannia glutinosa polysaccharide (RGP) on apoptosis of osteoarthritis (OA) chondrocytes induced by sodium iodoacetate (MIA) via the regulation of long-chain non-coding RNA (lncRNA) maternal expression gene 3 (MEG3). Methods　Rat chondrocytes were cultured with MIA 0, 1, 2, 4, and 8 μmol/ L to induce chondrocyte injury, and were then treated with RGP 50, 100, 200, 400, and 800 mg/ mL, respectively, to detect the appropriate experimental concentration. Rats were divided into a normal group, MIA group, RGP group, RGP+control (NC) small interfering RNA (siRNA) group, and RGP+si-MEG3 group. Cell viability was detected by Cell Counting Kit-8 (CCK-8) assay and apoptosis was detected by Hoechst 33258 staining and flow cytometry. mRNA levels of MEG3, metalloproteinase 13 (MMP-13), type Ⅱ collagen-α1 (COL2A1), and proteoglycan (ACAN) were detected by real-time quantitative polymerase chain reaction. Protein levels of PI3K, phospho (p) PI3K, serine/ threonine kinase(AKT), p-AKT, BAX, BCL-2, and caspase3 were detected by Western blot. Results 　MIA decreased chondrocyte viability and induced apoptosis in a dose-dependent manner, decreased MEG3, COL2A1, and ACAN mRNA levels, and increased MMP-13 mRNA levels (P<0. 05). RGP 100, 200, 400, and 800 mg/ mL increased chondrocyte viability and MEG3 levels (P <0. 05). Cell viability, MEG3, COL2A1, and ACAN mRNA, and p-PI3K/ PI3K, p-AKT/ AKT, and BCL-2 protein levels were decreased in the MIA group compared with the control group, while the apoptosis rate, MMP-13 mRNA, and BAX and caspase3 protein levels were increased (P<0. 05). Cell viability, MEG3, COL2A1, and ACAN mRNA, and p-PI3K/ PI3K, P-AKT/ AKT, and BCL-2 protein levels were increased in the RGP group compared with the MIA group, while the apoptosis rate, MMP-13 mRNA, and BAX and caspase3 protein levels were decreased (P<0. 05). Knockdown of MEG3 weakened the protective effect of RGP on MIA-induced chondrocyte injury. Conclusions　RGP can promote the synthesis of chondrocyte extracellular matrix and inhibit cell apoptosis and MIA-induced chondrocyte damage, possibly acting via a mechanism related to the up-regulation of MEG3 expression and induction of PI3K/ AKT pathway activation.

Abstract: Objective　To investigate the therapeutic effect and mechanism of Gubi powder on osteoarthritis. Methods　New Zealand white rabbits were divided into a blank group, model group, positive group (diclofenac potassium gel), and Gubi powder group (n = 6 rabbits per group). A rabbit knee osteoarthritis model was constructed using the modified Hulth method, and the treatments were administered for 4 weeks after 8 weeks of modeling. Cartilage thickness was measured by toluidine blue staining and the Mankin score was derived after Muscovite O staining of cartilage tissue. Terminal deoxynucleotidyl transferase dUTP nick end labeling fluorescence staining was used to detect the apoptosis of chondrocytes in cartilage tissue. Collagen (Col) Ⅱ and collagen X protein expression levels in cartilage tissue were detected by immunohistochemistry and expression levels of Bax, cleaved-caspase-3, phospho (p) extracellular signalregulated kinase (ERK), p-p38, p-Smad2, p-Smad3, and transforming growth factor (TGF)-β1 in cartilage tissues were detected by Western blot. Results　Cartilage thickness was decreased, the Mankin score and chondrocyte apoptosis rate were increased, Col Ⅱ, p-Smad2, p-Smad3, and TGF-β1 protein expression levels were decreased, and Col X, Bax, cleaved-caspase-3, p-ERK, and p-p38 levels were increased in the model group compared with the control group. Cartilage thickness was increased, the Mankin score and chondrocyte apoptosis rate were decreased, Col Ⅱ, p-Smad2, p-Smad3, and TGF-β1 expression levels were increased, and Col X, Bax, cleaved-caspase-3, p-ERK, and p-p38 protein expression were decreased in the positive and Gubi powder groups compared with the model group. Conclusions 　Gubi powder showed good therapeutic efficacy against osteoarthritis in rabbits, by reducing chondrocyte apoptosis, stabilizing cartilage tissue structure, and promoting the regeneration and repair of cartilage tissue after injury. Its mechanism may be related to inhibition of the ERK/ P38 pathway and activation of the TGF-β/ Smad pathway.

Abstract:In recent years, exosomes have been used as a medium for cell-cell communication, providing a new perspective for information exchange between cells. Exosomes from various cell types, such as mesenchymal stem cells, osteoblasts, osteoclasts, and their precursors, are play an important role in bone remodeling. Many studies have shown that common bone metabolic diseases, such as osteoporosis, fracture, and osteoarthritis, have obvious correlations with exocrine bodies. Although bisphosphonate drug treatment, autologous and allograft bone grafting, and other treatment method achieve good result , they may lead to various complications and adverse reactions. Therefore, it is very meaningful to develop new targeted therapies with a strong bone regeneration ability, lower complication rate, and more accuracy. Therefore, this article reviews the mechanism of exosomes from various sources acting on bone tissue cells and the application of related bone metabolism disease treatments to provide ideas for developing new bone regeneration treatment method.

Abstract: Objective To compare and analyze the differences between two commonly used modeling method for rabbit knee osteoarthritis (KOA) and provide references for the selection and establishment of different types of animal models for knee osteoarthritis. Methods Nine healthy New Zealand white rabbits were randomly divided into 3 groups: blank group, modified Hulth group and collagenase group. The model groups were treated with a modified Hulth method or intra-articular injection of collagenase. After 1 week, the rabbits were encouraged to move daily. After 6 weeks, they were evaluated using Lequesne MG scores, X-rays, micro-computed tomography, Pelletier scores, Mankin scores and enzyme- linked immunosorbent assays, and then the gross and pathological changes in the knee were observed. Results Compared with that in the blank group, the cartilage surface of the rabbit knee joints in the two model groups displayed defects. The pathological result showed that the cartilage layer appeared to be cracked, safranin O staining was decreased, the tide line was distorted, and the blood vessels passed. The concentrations of TNF-α in serum from the blank group, modified Hulth group, and collagenase group were (624. 99 ± 17. 82), (1140. 56 ± 129. 81) and (1480. 69 ± 492. 08) pg / mL, and the IL-1β concentrations in serum were (30. 23 ± 0. 25), (46. 67 ± 0. 71) and (46. 82 ± 1. 04) pg / mL, respectively. The modified Hulth and collagenase groups showed statistically significant differences compared with that in the blank group (all P<0. 05). In addition, the modified Hulth group was accompanied by osteophyte formation in the knee joint and more serious damage in the medial femoral condyle cartilage, while the medial tibial condyle was the main injury in the collagenase group. Conclusions Both modeling method can be used to construct an ideal KOA model. The degree of damage using the modified Hulth method was more serious, while the collagenase-induced model was closer to the process and pathogenesis of human KOA.

Abstract:Osteoarthritis (OA) is a chronic disease with a high disability rate. With the increase in the obesity rate and an aging patient population, OA is having more and more negative impacts on peoples lives and social resources. With the development of high-throughput technology, the study of non-coding RNA has gradually become a hot spot in the field of OA. Recent studies have shown that chondrocyte apoptosis and extracellular matrix degradation are the main pathological bases of OA. Non-coding RNA is closely related to chondrocytes, but the molecular mechanism has not been fully clarified. This article reviews the effects of non-coding RNA on chondrocytes and the extracellular matrix to further understand the mechanisms of cartilage degeneration and provide new ideas for the early diagnosis and treatment of OA.

Abstract:The NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome is involved in the pathogenesis of arthritis. Knee osteoarthritis (KOA) is considered to be an inflammatory disease. Increasing attention has been paid to the correlation between the NLRP3 inflammasome and KOA. The assembly and activation of the NLRP3 inflammasome produces a large number of pro-inflammatory factors and degradative enzymes, leading to cartilage destruction, synovial inflammation and pain onset. This review will summarize the evidence related to the involvement of the NLRP3 inflammasome pathway in KOA and its role in the pathology of osteoarthritis, with the aim of enhancing the management of KOA and providing new directions for the diagnosis and prevention of KOA.

Abstract:Knee osteoarthritis can be divided into primary and secondary types, but the etiology of these types is unknown. Animal experiments enable further exploring the pathogenesis and prevention of knee osteoarthritis. The related literature suggests that classic models can be divided into artificial induction and spontaneous modeling. The associated mainstream traditional Chinese medicine syndromes for this disease are kidney yang deficiency, blood stasis and cold dampness syndrome, which correspond to three modeling method . Animal models that combine these diseases and syndromes will be important for future research. These models, combined with the author’s practical experience in multiple modeling method , provide a review for reference.