Cartilage Protection Research Articles

Mechanical loading mitigates osteoarthritis symptoms by regulating the inflammatory microenvironment in a mouse model.

Osteoarthritis (OA) is one of the most common chronic diseases, in which inflammatory responses in the articular cavity induce chondrocyte apoptosis and cartilage degeneration. While mechanical loading is reported to mitigate synovial inflammation, the mechanism and pathways for the loading-driven improvement of OA symptoms remain unclear. In this study, we evaluated the loading effects on M1/M2 polarization of synovial macrophages via performing histology, cytology, and molecular analyses. In the OA group, the cell layer of the synovial lining was enlarged with an increase in cell density. Also, M1 macrophages were polarized and proinflammatory cytokines were increased. In contrast, in the OA group with mechanical loading, cartilage degradation was reduced and synovial inflammation was alleviated. Notably, the M1 macrophages were diminished by mechanical loading, while M2 macrophages were increased. Furthermore, mechanical loading decreased the levels of proinflammatory cytokines, such as interleukin-1 beta and tumor necrosis factor-α, and suppressed PI3K/AKT/NF-κB signaling. Taken together, this study demonstrates that mechanical loading changes the ratio of M1 and M2 macrophages via regulation of PI3K/AKT/NF-κB signaling and provides cartilage protection in the mouse OA model.

Icariin-Loaded Hydrogel Regulates Bone Marrow Mesenchymal Stem Cell Chondrogenic Differentiation and Promotes Cartilage Repair in Osteoarthritis.

Intra-articular injection of mesenchymal stem cells is a potential therapeutic strategy for cartilage protection and symptom relief for osteoarthritis (OA). However, controlling chondrogenesis of the implanted cells in the articular cavity remains a challenge. In this study, hydrogels containing different concentrations of icariin were prepared by in situ crosslinking of hyaluronic acid and Poloxamer 407. This injectable and thermoresponsive hydrogel, as a 3D cell culture system, showed good biocompatibility with chondrocytes and bone marrow mesenchymal stem cells (BMSCs), as well as promoted proliferation and chondrogenesis of BMSCs through the Wnt/β-catenin signaling pathway. Intra-articular injection of this kind of BMSC-loaded composite hydrogel can significantly prevent cartilage destruction by inducing chondrogenic differentiation of BMSCs, and relieve pain through regulating the expression of inflammatory cytokines (e.g., IL-10 and MMP-13) in the OA model. Incorporating BMSCs into this novel icariin-loaded hydrogel indicates a more superior efficacy than the single BMSC injection, which suggests a great potential for its application in OA.

Network Pharmacology and Molecular Docking Study of the Chinese Miao Medicine Sidaxue in the Treatment of Rheumatoid Arthritis.

PurposeThis study aimed to investigate the molecular mechanisms of Compound Sidaxue (SX), a prescription of Chinese Miao medicine, in treating rheumatoid arthritis (RA) using network pharmacology and in vivo experimental approaches.MethodsNetwork pharmacology was adopted to detect the active components of four Traditional Chinese herbal medicine (TCM) of SX, and the key targets and signaling pathways in the treatment of RA were predicted, and the key components and targets were screened for molecular docking. The predicted targets and pathways were validated in bovine type II collagen and incomplete Freund’s adjuvant emulsifier-induced rat RA model.ResultsIn this study, we identified 33 active components from SX, predicted to act on 44 RA-associated targets by network pharmacology. PPI network demonstrated that TNF-α, VEGF-A, IL-2, IL-6, AKT, PI3K, STAT1 may serve as the key targets of SX for the treatment of RA. The main functional pathways involving these key targets include PI3K-AKT signaling pathway, TNF signaling pathway, NF-κB signaling pathway. Molecular docking analysis found that the active components β-amyrin, cajanin, eleutheroside A have high affinity for TNF-α, VEGFA, IL-2, AKT, and PI3K, etc. SX can improve joint swelling in Collagen-induced arthritis (CIA) rats, reduce inflammatory cell infiltration and angiogenesis in joint synovial tissue, and down-regulate IL-2, IL-6, TNF-α, VEGF, PI3K, AKT, p-AKT, NF-κBp65, the expression of p-NF-κBp65, STAT1, and PTGS2 are used to control the exacerbation of inflammation and alleviate the proliferation of synovial pannus, and at the same time play the role of cartilage protection to achieve the effect of treating RA.ConclusionThrough a network pharmacology approach and animal study, we predicted and validated the active compounds of SX and their potential targets for RA treatment. The results suggest that SX can markedly alleviate CIA rat by modulating the VEGF/PI3K/AKT signaling pathway, TNF-α signaling pathway, IL/NF-κB signaling pathway.

Pharmacology and molecular docking study of cartilage protection of Chinese herbal medicine Fufang Shatai Heji (STHJ) by inhibiting the expression of MMPs in collagen-induced arthritis mice.

This study aims to explore whether Fufang Shatai Heji (STHJ), as a mixture collected by a decoction of a variety of Chinese herbal medicines for immune system diseases, can improve the cartilage destruction of rheumatoid arthritis (RA). The therapeutic effects of STHJ were studied using collagen induced arthritis (CIA) mice. The improvement effect of STHJ on synovitis and cartilage damage caused by arthritis was studied by joint pathological analysis. The inhibitory effect of STHJ on related degradation enzymes in cartilage was studied by immunohistochemistry and real-time polymerase chain reaction (PCR). The specific targets of STHJ were predicted by molecular docking. After successfully inducing CIA, the paws of the mice showed significant swelling, and athological analysis of the ankle and knee joints also showed significant cartilage destruction and synovial hyperplasia. However, synovial hyperplasia and cartilage destruction were markedly alleviated after administration of STHJ. And after STHJ treatment, the expression of ADAMTS-4, ADAMTS-5, MMP-9 and MMP-13, in the cartilage layer of CIA mice was significantly inhibited. Through molecular docking assays, we proved that acteoside in STHJ could directly bind to the Glu111, Phe110 residues in MMP-9 and glycyrrhizic acid in STHJ bind to the Glu382, Asn433 residues in MMP-13. Our results suggested that STHJ may alleviate synovial hyperplasia and cartilage destruction in CIA mice and protect cartilage by inhibiting the expression of MMP-9 and other enzymes.

Combination of mesenchymal stem cells and bioactive molecules in hydrogels for osteoarthritis treatment

Osteoarthritis (OA) is a chronic and inflammatory disease with no effective regenerative treatments to date. The therapeutic potential of mesenchymal stem cells (MSCs) remains to be fully explored. Intra-articular injection of these cells promotes cartilage protection and regeneration by paracrine signaling and differentiation into chondrocytes. However, joints display a harsh avascular environment for these cells upon injection. This phenomenon prompted researchers to develop suitable injectable materials or systems for MSCs to enhance their function and survival. Among them, hydrogels can absorb a large amount of water and maintain their 3D structure but also allow incorporation of bioactive agents or small molecules in their matrix that maximize the action of MSCs. These materials possess advantageous cartilage-like features such as collagen or hyaluronic acid moieties that interact with MSC receptors, thereby promoting cell adhesion. This review provides an up-to-date overview of the progress and opportunities of MSCs entrapped into hydrogels, combined with bioactive/small molecules to improve the therapeutic effects in OA treatment.

Exosomes derived from platelet-rich plasma administration in site mediate cartilage protection in subtalar osteoarthritis

Subtalar osteoarthritis (STOA) is often secondary to chronic ankle sprains, which seriously affects the quality of life of patients. Due to its etiology and pathogenesis was not studied equivocally yet, there is currently a lack of effective conservative treatments. Although they have been used for tissue repair, platelet-rich plasma-derived exosomes (PRP-Exo) have the disadvantage of low retention and short-lived therapeutic effects. This study aimed to determine whether incorporation of PRP-Exo in thermosensitive hydrogel (Gel) increased their retention in the joint and thereby playing a therapeutic role on STOA due to chronic mechanical instability established by transecting lateral ligaments (anterior talofibular ligament (ATFL)/calcaneal fibular ligament (CFL)). PRP-Exo incorporated Gel (Exo-Gel) system, composed of Poloxamer-407 and 188 mixture-based thermoresponsive hydrogel matrix in an optimal ratio, was determined by its release ability of Exo and rheology of Gel response to different temperature. The biological activity of Exo-Gel was evaluated in vitro, and the therapeutic effect of Exo-Gel on STOA was evaluated in vivo. Exo released from Exo-Gel continuously for 28 days could promote the proliferation and migration of mouse bone mesenchymal stem cells (mBMSCs) and chondrocytes, at the same time enhance the chondrogenic differentiation of mBMSCs, and inhibit inflammation-induced chondrocyte degeneration. In vivo experiments confirmed that Exo-Gel increased the local retention of Exo, inhibited the apoptosis and hypertrophy of chondrocytes, enhanced their proliferation, and potentially played the role in stem cell recruitment to delay the development of STOA. Thus, Delivery of PRP-Exo incorporated in thermosensitive Gel provides a novel approach of cell-free therapy and has therapeutic effect on STOA.Graphical

The ROS‐responsive scavenger with intrinsic antioxidant capability and enhanced immunomodulatory effects for cartilage protection and osteoarthritis remission

Oxidative stress has close relationship with the progression of osteoarthritis and thus is an important therapeutic target. The use of antioxidants alone has common disadvantages such as low bioavailability, poor stability, and rapid joint clearance or toxicity at high concentrations. To achieve both reactive oxygen species (ROS) responsive scavenging ability and drug targeted delivery ability, a novel polymer (PEG-PTK-PEG) was synthesized through a simple and direct reaction between polythioketal (PTK) and m-PEG-acrylate. In addition to excellent mechanical properties and high drug loading capacity, the degradation products of PEG-PTK-PEG responding to the ROS accumulating microenvironment also have excellent biocompatibility and extremely low toxicity. Further, the PEG-PTK-PEG nanoparticles (NPs) loaded with astaxanthin (ASTA), which is an antioxidant with high biological safety, could effectively reduce ROS expression and release ASTA slowly and accurately in the area of high ROS expression as a result of the polymer degradation. In the OA model, the PEG-PTK-PEG@ASTA could effectively inhibit the expression of ROS, thereby downregulating the MAPK signaling pathway and inducing the conversion of macrophages from the M1 phenotype to the M2 phenotype. The synergistic effect of PEG-PTK-PEG's ROS-responsive drug delivery ability and ROS scavenging ability significantly promoted the therapeutic effect of OA, providing a new and effective strategy for the clinical treatment of OA.

Stiffness- and Bioactive Factor-Mediated Protection of Self-Assembled Cartilage against Macrophage Challenge in a Novel Co-Culture System.

Objective:Tissue-engineered cartilage implants must withstand the potential inflammatory and joint loading environment for successful long-term repair of defects. The work’s objectives were to develop a novel, direct cartilage-macrophage co-culture system and to characterize interactions between self-assembled neocartilage and differentially stimulated macrophages.Design:In study 1, it was hypothesized that the proinflammatory response of macrophages would intensify with increasing construct stiffness; it was expected that the neocartilage would display a decrease in mechanical properties after co-culture. In study 2, it was hypothesized that bioactive factors would protect neocartilage properties during macrophage co-culture. Also, it was hypothesized that interleukin 10 (IL-10)-stimulated macrophages would improve neocartilage mechanical properties compared to lipopolysaccharide (LPS)-stimulated macrophages.Results:As hypothesized, stiffer neocartilage elicited a heightened proinflammatory macrophage response, increasing tumor necrosis factor alpha (TNF-α) secretion by 5.47 times when LPS-stimulated compared to construct-only controls. Interestingly, this response did not adversely affect construct properties for the stiffest neocartilage but did correspond to a significant decrease in aggregate modulus for soft and medium stiffness constructs. In addition, bioactive factor-treated constructs were protected from macrophage challenge compared to chondrogenic medium-treated constructs, but IL-10 did not improve neocartilage properties, although stiff constructs appeared to bolster the anti-inflammatory nature of IL-10-stimulated macrophages. However, co-culture of bioactive factor-treated constructs with LPS-treated macrophages reduced TNF-α secretion by over 4 times compared to macrophage-only controls.Conclusions:In conclusion, neocartilage stiffness can mediate macrophage behavior, but stiffness and bioactive factors prevent macrophage-induced degradation. Ultimately, this co-culture system could be utilized for additional studies to develop the burgeoning field of cartilage mechano-immunology.

Relationship between Osteoarthritis and Endocrine Disease in KSA: A Cross-Sectional Study

Background: Osteoarthritis (OA), the most common kind of arthritis, affects millions of people throughout the world. This problem occurs when the protective cartilage that cushions the ends of the bones wears away over time. The goal of this study was to draw attention to the link between osteoarthritis and a number of endocrine illnesses in the Saudi population.
 Methods: This was a cross-sectional research with the goal of shedding light on the link between osteoarthritis and endocrine problems. The research was conducted in Saudi Arabia at colleges, hospitals, and shopping centers. During the months of June to November 2021, data was collected from patients and the general public.
 Results: The study included 743 participants. Among them, there were, 519 females (69.9%) and 224 males (30.1%). The most prevalent age group was 20-30 years (n= 354, 47.6%). Majority of study participants were Saudi (n= 713, 96%) and the rest were non-Saudi. The mean body mass index (BMI) among study participants was 29.47 + 7.53 with median BMI of 30 kg/m2. It was found that 85 participants took anti-inflammatory drugs for more than twice per week during the last three months (11.4%). It is noticed that the prevalence of autoimmune disease among study participants is low. However, female participants were higher in hypothyroid (P= 0.001).
 Conclusion: Finally, it appears that weight, rather than IR, explains the relationship between endocrine disease and knee OA. Individuals with arthritic knee pain may benefit from endocrine disease therapy since the accumulation of endocrine disease components is connected to a higher degree of knee discomfort, independent of age, sex, or weight.

Comparison of Curative Effect of Human Umbilical Cord-Derived Mesenchymal Stem Cells and Their Small Extracellular Vesicles in Treating Osteoarthritis.

IntroductionHuman umbilical cord-derived mesenchymal stem cells (hUC-MSCs) and their small extracellular vesicles (hUC-MSC-sEVs) have shown attractive prospects applying in regenerative medicine. This study aimed to compare the therapeutic effects of two agents on osteoarthritis (OA) and investigate underlying mechanism using proteomics.MethodsIn vitro, the proliferation and migration abilities of chondrocytes treated with hUC-MSCs or hUC-MSC-sEVs were detected by Cell Counting Kit-8 assay and scratch wound assay. In vivo, hUC-MSCs (a single dose of 5 × 105) or hUC-MSC-sEVs (30 μg/time) were injected into the knee joints of anterior cruciate ligament transection-induced OA model. Hematoxylin and eosin, Safranin O/Fast Green staining were used to observe cartilage degeneration. The levels of cartilage matrix metabolic molecules (Collagen II, MMP13 and ADAMTS5) and macrophage polarization markers (CD14, IL-1β, IL-10 and CD206) were assessed by immunohistochemistry. Finally, proteomics analysis was performed to characterize the proteinaceous contents of two agents.ResultsIn vitro data showed that hUC-MSC-sEVs were taken up by chondrocytes. A total of 15 μg/mL of sEVs show the greatest proliferative and migratory capacities among all groups. In the animal study, hUC-MSCs and hUC-MSC-sEVs alleviated cartilage damage. This effect was mediated via maintaining cartilage homeostasis, as was confirmed by upregulation of the COL II and downregulation of the MMP13 and ADAMTS5. Moreover, the M1 macrophage markers (CD14) were significantly reduced, while the M2 macrophage markers (CD206 and IL-10) were increased in the hUC-MSCs and hUC-MSC-sEVs relative to the untreated group. Mechanistically, we found that many proteins connected to cartilage repair were more abundant in sEVs. Notably, compared to hUC-MSCs, the upregulated proteins in sEVs were mostly involved in the regulation of immune effector process, extracellular matrix organization, PI3K-AKT signaling pathways, and Rap1 signaling pathway.ConclusionOur study indicated that hUC-MSC-sEVs protect cartilage from damage and many cartilage repair-related proteins are probably involved in the restoration process. These data suggest the promising potential of hUC-MSC-sEVs as a therapeutic agent for OA.

Kartogenin Promotes the BMSCs Chondrogenic Differentiation in Osteoarthritis by Down-Regulation of miR-145-5p Targeting Smad4 Pathway.

Transplantation of mesenchymal stem cells (MSCs) is a potential therapeutic strategy for cartilage degeneration of osteoarthritis (OA). But controlling chondrogenic differentiation of the implanted MSCs in the joints remains a challenge. The role of kartogenin (KGN) for chondrogenesis of MSCs has been widely reported, however, the mechanism of chondrogenesis has not been elucidated in OA. In this study, we investigated the miR-145-5p, TGF-β, Samd4, and p-stat3/stat3 expression in cartilage of OA patients and bone marrow mesenchymal stem cells (BMSCs) treated with KGN or miR-145-5p inhibitor. In addition, the cell proliferation and chondrogenic differentiation in vitro and in vivo of BMSCs treated with KGN was also detected. In OA patients, the expression of miR-145-5p was up-regulated, and the expression of TGF-β, Samd4, and p-stat3/stat3 was inhibited. When the BMSCs treated with miR-145-5p inhibitor, the expression of TGF-β, Samd4, and p-stat3/stat3 was also significantly up-regulated. KGN-treated BMSCs had better proliferation and chondrogenic differentiation by up-regulating the expression of Sox 9, Col-2a1, aggrecan in vitro and in OA by down-regulation of miR-145-5p targeting Smad4 pathway. Moreover, intra-articular injection of KGN-treated BMSCs had a better pain relief effect in OA. The double effect on cartilage protection and pain relief indicates a great potential of intra-articular injection of KGN-treated BMSCs for the treatment of OA.

Supercritical carbon dioxide decellularized porcine cartilage graft with PRP attenuated OA progression and regenerated articular cartilage in ACLT-induced OA rats.

Knee osteoarthritis (OA) is a common degenerative articular disorder and considered one of the primary causes of pain and functional disability. Knee OA is prevalent in 10% of men and 13% of women aged 60years above. The study aims to use cartilage tissue engineering that combines the triads of decellularized porcine cartilage graft as "scaffold," plasma rich platelet (PRP) as "signal" and chondrocytes from rat as "cell" to attenuate ACLT-induced OA progression and regenerate the knee cartilage in rats. Decellularization of the porcine cartilage was characterized by hematoxylin and eosin, 4,6-Diamidino-2-phenylindole staining, scanning electron microscopy and residual DNA quantification. The protective effect of decellularized porcine cartilage graft (dPCG) was evaluated by intra-articular administration in surgically induced anterior cruciate ligament transection (ACLT) rat osteoarthritis (OA) model. Supercritical carbon dioxide technology completely decellularized the porcine cartilage. Intra-articular administration of dPCG with or without PRP significantly reduced the ACLT-induced OA symptoms and attenuated the OA progression. Pain-relief by dPCG with or without PRP was assessed by capacitance meter and improved articular cartilage damage in the rat knee was characterized by X-ray and micro-CT. Besides, the histological analysis depicted cartilage protection by dPCG with or without PRP. The repairation and attenuation effect by dPCG with or without PRP in the articular knee cartilage damage were also explored by safranin-O, type II collagen, aggrecan and SOX-9 immuno-staining. To conclude, intra-articular administration of dPCG with or without PRP is efficient in repairing the damaged cartilage in the experimental OA model.

Effectiveness of the Self-Care Sandbag Exercise Program for the Osteoarthritis of Knee Patients in the Secondary Care in Thailand: Randomized Control Trial

Osteoarthritis is the most common form of arthritis in the knee. It is occurring when the protective cartilage that cushions the ends of your bones wears down over time and mostly often in people 50 years of age and older. The study was designed to randomized control trial and aimed to compare before and after the 3-months intervention program on self-care sandbag exercise program for knee osteoarthritis patients in the secondary care in Thailand. They were divided into 2 groups, the intervention group, and the control group by using the probability sampling. Seventy knee osteoarthritis patients participated in this study. Both of group were assessed the Oxford knee score and the knowledge of knee osteoarthritis at the baseline and after 3-months intervention program. The Independent t-test and Paired sample t-test were used for comparison the all parameters between and within the group, respectively. The results showed that the Oxford pain score of knee osteoarthritis was decreased scientifically more than the control group (p<0.001) and the knowledge of knee osteoarthritis was increased significantly (p<0.001). In conclusion, the self-care sandbag exercise program can reduce the severity of pain among knee osteoarthritis patients and can promote to the usaul care for the osteoarthritis pateintes.

Intra-Articular Injection of miR-29a-3p of BMSCs Promotes Cartilage Self-Repairing and Alleviates Pain in the Rat Osteoarthritis.

Stem cells intra-articular injection stagey indicated a potential therapeutic effect on improving the pathological progress of osteoarthritis (OA). However, the long-term effect of stem cells intra-articular injection on the cartilage regeneration remains unclear. miR-29a-3p is predicted to be a critical target for inhibiting insulin-like growth factor-1 expression and may aggravate the progression of OA. In this study, we investigated the therapeutic efficacy of intra-articular injection of bone marrow mesenchymal stem cells (BMSCs) transfected with miR-29a-3p inhibitor in OA. miR-29a-3p inhibitor transfection did not influence cell viability of BMSCs, while the chondrogenic differentiation potential of BMSCs was significantly improved. Interestingly, intra-articular injection of BMSCs with miR-29a-3p inhibition significantly prevented articular cartilage degeneration by up-regulating the expression of Sox 9, Col-2a1, aggrecan and down-regulating the expression of matrix metalloproteinase, as well as relieved pain in OA. The double effects on cartilage protection and pain relief indicated a great potential of intra-articular injection of miR-29a-3p inhibitor-transfected BMSCs for the treatment of OA.

Nootkatone protects cartilage against degeneration in mice by inhibiting NF-κB signaling pathway

Osteoarthritis is a common chronic disease associated with chondrocyte inflammation and cartilage matrix hydrolyzation. Studies report that IL-1β plays a critical role in osteoarthritis. Anti-inflammatory effect of nootkatone has been explored in acute and chronic inflammatory disease, thus the current study sought to explore its therapeutic effect in osteoarthritis. Notably, the effect of nootkatone in osteoarthritis has not been elucidated. Therefore, murine primary chondrocytes were extracted and ACLT induced OA mouse model was established in the current study to explore the therapeutic effect of nootkatone in OA both in vitro and in vivo. The findings showed that nootkatone inhibited inflammatory response and protected cartilage balance in murine primary chondrocyte. Further analysis showed that nootkatone suppressed inflammation and protected cartilage against degeneration induced by ACLT surgery in mice. The cellular mechanism of the protective effect of nootkatone in osteoarthritis and associated signaling pathway was identified as the NF-κB signaling pathway. In summary, the findings of the current study indicated that nootkatone is a potential therapeutic agent for OA.

Therapeutic evaluation of galangin on cartilage protection and analgesic activity in a rat model of osteoarthritis

Osteoarthritis (OA) is a form of arthritis due to degradation of articular cartilage. OA is associated with stiffness, joint pain, and dysfunction, affecting adults worldwide. Galangin is a bioactive flavonoid that exerts several therapeutic and biological activities. Anti-hyperglycemic, anti-inflammatory, anti-cancer, and anti-apoptotic activities of galangin have been reported in several studies. In the present study, rats were divided into normal control, OA (control), galangin 10 mg/kg (low-dose), galangin 100 mg/kg (high-dose), and celecoxib 30 mg/kg (positive control) groups. All doses were administered orally for 14 consecutive days. The urinary type II collagen (µCTX-II) level as well as reactive oxygen species, tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6, superoxide dismutase, catalase, lipid peroxidation, reduced glutathione, and glutathione peroxidase levels were measured. In addition, the CTX-II mRNA and protein expression levels were measured. Galangin supplementation significantly reduced the µCTX-II level compared with controls. Galangin treatment significantly reduced reactive oxygen species, lipid peroxidation, interleukin-1 beta, interleukin-6, and tumor necrosis factor-alpha levels, but increased catalase, superoxide dismutase, glutathione peroxidase, and reduced glutathione levels. Galangin treatment significantly reduced the CTX-II mRNA and protein expression levels. The low CTX-II level in tissue indicated the inhibition of cartilage degradation. In summary, supplementation with galangin was effective against OA. The identification of potential therapeutic agents that inhibit inflammation may be useful for the management and prevention of OA. How to cite: Su Y, Shen L, Xue J, et al. Therapeutic evaluation of galangin on cartilage protection and analgesic activity in a rat model of osteoarthritis. Electron J Biotechnol 2021;53. https://doi.org/10.1016/j.ejbt.2021.05.005

Amelioration of post-traumatic osteoarthritis via nanoparticle depots delivering small interfering RNA to damaged cartilage.

The progression of osteoarthritis (OA) is associated with inflammation triggered by the enzymatic degradation of extracellular matrix in injured cartilage. Here, we show that a locally injected depot of nanoparticles functionalized with an antibody targeting collagen type-II and carrying small interfering RNA for matrix metalloproteinase 13 (MMP13), which breaks down collagen type-II, substantially reduced the expression of MMP13 and protected cartilage integrity and overall joint structure in acute and severe mouse models of post-traumatic OA. MMP13 inhibition suppressed clusters of genes associated with tissue restructuring, angiogenesis, innate immune responses and proteolysis. We also show that intra-articular injections of the nanoparticles led to higher reductions in disease progression than either a single injection or weekly injections of the steroid methylprednisolone. Sustained drug retention by targeting collagen in the damaged extracellular matrix of osteoarthritic cartilage may also be an effective strategy for the treatment of OA with other disease-modifying drugs.

Both microRNA-455-5p and -3p repress hypoxia-inducible factor-2\u03b1 expression and coordinately regulate cartilage homeostasis

Osteoarthritis (OA), the most common aging-related joint disease, is caused by an imbalance between extracellular matrix synthesis and degradation. Here, we discover that both strands of microRNA-455 (miR-455), -5p and -3p, are up-regulated by Sox9, an essential transcription factor for cartilage differentiation and function. Both miR-455-5p and -3p are highly expressed in human chondrocytes from normal articular cartilage and in mouse primary chondrocytes. We generate miR-455 knockout mice, and find that cartilage degeneration mimicking OA and elevated expression of cartilage degeneration-related genes are observed at 6-months-old. Using a cell-based miRNA target screening system, we identify hypoxia-inducible factor-2α (HIF-2α), a catabolic factor for cartilage homeostasis, as a direct target of both miR-455-5p and -3p. In addition, overexpression of both miR-455-5p and -3p protect cartilage degeneration in a mouse OA model, demonstrating their potential therapeutic value. Furthermore, knockdown of HIF-2α in 6-month-old miR-455 knockout cartilage rescues the elevated expression of cartilage degeneration-related genes. These data demonstrate that both strands of a miRNA target the same gene to regulate articular cartilage homeostasis.

Efficacy Treatment of Osteoarthritis with Combine Chondroitin and Glucosamine.

Osteoarthritis led to the articular cartilage damage and cause different kind of problems - from social to biological. The analysis of existing research unfortunately subjected questioned the reliability of spontaneous regeneration of damaged cartilage, which makes it necessary to focus on the possibilities of protection of the tissue from further its degradation. Treatment of osteoarthritis require to use many drugs, which would lead to slowdown the this process. The aim of below publication is to analyse the practical, clinical biological possibilities of articular cartilage protection with a usage of SYSADOA - (symptomatic slow acting drugs of OA). Osteoarthritis is most frequent disease of the joints and prescription of the SYSADOA should be main principle of that treatment.

Research progress of curcumin in the treatment of osteoarthritis

Curcumin is the main active component of Curcuma longa,which has a variety of biological activities and pharmacological properties.Clinical studies have shown that curcumin and its derivatives can improve the pathological progress of osteoarthritis. The mechanism mainly includes enhancing the activity of antioxidant enzymes,inhibiting oxidative stress,and protecting cartilage from damage;blocking inflammation-related signal pathways,reducing the production and activity of inflammatory factors,and reducing inflammation;playing the role of immune regulation by interacting with immune cells and immune molecules;slowing down osteoarthritis by inhibiting chondrocyte apoptosis and enhancing cartilage protection. Curcumin is one of the potential drugs for the treatment of osteoarthritis.