Tenosynovial giant cell tumor: a case report.

BACKGROUND: This case reports the synchronous diagnosis of two rare unrelated diseases; leiomyosarcoma and tenosynovial giant cell tumor of the knee. It focuses on the challenges of diagnosing tenosynovial giant cell tumor, including cognitive biases in clinical medicine that delay diagnosis. It also demonstrates the pathogenic etiology of tenosynovial giant cell tumor, evidenced by the transient deterioration of the patients' knee symptoms following the administration of prophylactic granulocyte colony-stimulating factor given as part of the chemotherapeutic regime for leiomyosarcoma. CASE PRESENTATION: A 37-year-old Caucasian man presented with a left groin lump and left knee pain with swelling and locking. Investigations including positron emission tomography-computed tomography and biopsy revealed leiomyosarcoma in a lymph node likely related to the spermatic cord, with high-grade uptake in the left knee that was presumed to be the primary site. His knee symptoms temporarily worsened each time granulocyte colony-stimulating factor was administered with each cycle of chemotherapy for leiomyosarcoma to help combat myelosuppressive toxicity. Subsequent magnetic resonance imaging and biopsy of the knee confirmed a tenosynovial giant cell tumor. His knee symptoms relating to the tenosynovial giant cell tumor improved following the completion of his leiomyosarcoma treatment. CONCLUSIONS: Tenosynovial giant cell tumor remains a diagnostic challenge. We discuss the key clinical features and investigations that aid prompt diagnosis. The National Comprehensive Cancer Network clinical practice guidelines for soft tissue sarcoma have recently been updated to include the pharmacological management of tenosynovial giant cell tumor. Our case discussion provides an up-to-date review of the evidence for optimal management of patients with tenosynovial giant cell tumor, with a particular focus on novel pharmacological options that exploit underlying pathogenesis.

Tuina Manipulation to Reduce Inflammation and Cartilage Loss in Knee Osteoarthritis Rats.

Clinical trials suggest that Tuina manipulation is effective in treating knee osteoarthritis (KOA), while further studies are required to discover its mechanism. Therefore, the manipulation of animal models of knee osteoarthritis is critical. This protocol provides a standard process for Tuina manipulation on KOA rats and a preliminary exploration of the mechanism of Tuina for KOA. The press and kneading manipulation method (a kind of Tuina manipulation that refers to pressing and kneading the specific area of the body surface) is applied on 5 acupoints around the knee joint of rats. The force and frequency of the manipulation were standardized by finger pressure recordings, and the position of the rat during manipulation is described in detail in the protocol. The effect of manipulation can be measured by pain behavior tests and microscopic findings in synovial and cartilage. KOA rats showed significant improvement in pain behavior. The synovial tissue inflammatory infiltration was reduced in the Tuina group, and the expression of tumor necrosis factor (TNF)-α was significantly lower. Compared to the control group, chondrocyte apoptosis was less in the Tuina group. This study provides a standardized protocol for Tuina manipulation on KOA rats and preliminary proof that the therapeutic effects of Tuina may be related to reducing synovial inflammation and delayed chondrocyte apoptosis.

Associations Between Dietary Intake of Vitamin K and Changes in Symptomatic and Structural Changes in Patients With Knee Osteoarthritis.

OBJECTIVE: To investigate associations of dietary vitamin K intake with changes in knee symptoms and structures in patients with knee osteoarthritis (OA). METHODS: Participants with symptomatic knee OA were enrolled (n = 259) and followed up for 2 years (n = 212). Baseline dietary vitamin K intake was calculated from a validated food frequency questionnaire. Knee symptoms were assessed by using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores. Knee cartilage defects, bone marrow lesions, and effusion-synovitis volume were measured from magnetic resonance imaging (MRI) scans. Univariable and multivariable linear regressions were used for analyses. RESULTS: A higher vitamin K intake quartile was significantly associated with a greater decrease in the total WOMAC score and dysfunction score over 24 months. The subgroup analyses showed in patients with severe baseline visual analog scale (VAS) pain that a higher vitamin K intake quartile was associated with more improvement in all WOMAC scores. There were no overall significant associations between vitamin K intake and changes in MRI features. In subgroup analysis, vitamin K intake was negatively associated with changes in tibiofemoral, patellar, and total cartilage defects in participants with a severe baseline radiographic grade and was negatively associated with change in total and patellar cartilage defects in participants with severe baseline VAS pain and in female patients. CONCLUSION: The association of higher vitamin K intake with decreased knee symptoms over 24 months in patients with knee OA suggests that clinical trials examining the effect of vitamin K supplementation for knee OA symptoms are warranted. Whether there is an effect on knee structure is unclear.

Effects of Combined Allogenic Adipose Stem Cells and Hyperbaric Oxygenation Treatment on Pathogenesis of Osteoarthritis in Knee Joint Induced by Monoiodoacetate.

The beneficial effects of HBO in inflammatory processes make it an attractive type of treatment for chronic arthritis. In addition, the effects of combination therapy based on adipose stem cells and HBO on OA progression have not been fully investigated. The current study explored the efficacy of intra-articular injection of allogeneic adipose-derived mesenchymal stem cells (ADMSCs) combined with hyperbaric oxygenation treatment (HBO) in a rat osteoarthritis (OA) model. The rat OA model was induced by intra-articular injection of monoiodoacetate (MIA) and 7 days after application of MIA rats were divided into five groups: healthy control (CTRL), osteoarthritis (OA), ADMSCs (ADS), the HBO+ADS21day and HBO+ADS28day groups. A single dose of 1 × 106 allogeneic ADMSCs suspended in sterile saline was injected into the knee joint alone or in combination with HBO treatment. Rats were sacrificed at 3 or 4 weeks after MIA injection. Treatment outcomes were evaluated by radiographic, morphological and histological analysis and by specific staining of articular cartilage. We also measured the level of inflammatory and pro/antioxidative markers. We confirmed that combined treatment of ADMSCs and HBO significantly improved the regeneration of cartilage in the knee joint. Rtg score of knee joint damage was significantly decreased in the HBO+ADS21day and HBO+ADS28day groups compared to the OA. However, the positive effect in the HBO+ADS28day group was greater than the HBO+ADS21day group. The articular cartilage was relatively normal in the HBO+ADS28day group, but moderate degeneration was observed in the HBO+ADS21day compared to the OA group. These findings are in line with the histopathological results. A significantly lower level of O2-. was observed in the HBO+ADS28day group but a higher NO level compared to the HBO+ADS21day group. Moreover, in the HBO+ADS28day group significantly higher concentrations of IL-10 were observed but there was no significant difference in proinflammatory cytokine in serum samples. These results indicate that a single intra-articular injection of allogeneic ADMSCs combined with HBO efficiently attenuated OA progression after 28 days with greater therapeutic effect compared to alone ADMSCs or after 3 weeks of combined treatment. Combined treatment might be an effective treatment for OA in humans.

Which part of the blood in the knee joint is responsible for its detrimental effects? (An experimental study on the knee joint in rabbits).

AIM: This study aims to determine the potential causative elements which are responsible for the cartilage damage in case of frequent intra-articular bleeding and to evaluate the effects of intra-articular free iron and chelation of iron in the knee joint. METHODS: Thirty-five New Zealand rabbits were randomly divided into five groups according to substances injected into their knee joints. Plasma (group I) and cellular components (group II) of the blood harvested from the rabbits, iron (ferric hydroxide sucrose) (group III), iron&chelator (group IV) and only chelator (deferoxamine mesylate) (group V) were injected into their right knees three times a week for 12 weeks. The joint surface was examined histologically according to the classification system modified from Colombo et al. The changes in the synovial tissue were evaluated according to the scoring system modified from Madhok et al. RESULTS: Cartilage and synovial abnormality scores were significantly higher in all study groups when compared to their own controls (p < 0.0001). Cartilage scores of groups I and V were significantly lower when compared to groups III and IV (p = 0.002 for group I and p = 0.003 for group V). Synovial abnormality score of group I was significantly lower than scores of groups III and IV (p = 0.001); and of group V lower than groups III and IV (p = 0.003 and p = 0.001, respectively). CONCLUSIONS: All substances tested in this study caused a certain amount of damage in the cartilage tissue and led to synovial abnormalities. Both iron and iron&chelator caused more damage in the cartilage and led to more advanced synovial changes when compared to the plasma component of blood and chelator itself. Influence of iron and iron&chelators were found to be similar showing that chelation was inadequate in antagonizing the detrimental effects of iron.

Intra-articular ozone slows down the process of degeneration of articular cartilage in the knees of rats with osteoarthritis.

BACKGROUND: Osteoarthritis (OA) is a joint disease of multifactorial etiology, affecting mainly the knees. We aimed to evaluate the effects of two different doses of gaseous ozone intra-articularly on the knee cartilage morphology of rats with osteoarthritis (OA). METHODS: The articular lesion was induced by sodium monoiodoacetate (MIA). 40 Wistar rats were divided into 4 groups: G1 control (without lesion and without treatment), G2 articular lesion (AL) (only lesion MIA-induced), G3 AL + treatment with 5 µg/mL of ozone intra-articular, and G4 AL + treatment with 10 µg/mL of ozone intra-articular. The experiment was carried out for 60 days. RESULTS: Both doses of ozone intra-articular demonstrated less reduction in joint space (G3 and G4) compared to the G2, formation of osteophytes, but without subchondral sclerosis. Ozone decreased the volumetric density of the articular lesion (VV(AL)) of tibial. The treatments recovered VV(AL) of the femur similar to G1. Ozone lower dose (G3) showed lower tibia and femur macroscopic scores. CONCLUSION: Intra-articular gaseous ozone can delay the degeneration of articular cartilage and can represents an integrative therapy in the OA treatment of knee after 60 days of treatment. For the first time the role of ozone in articular cartilage degeneration was evaluated helping to understand this therapy.

Metabolism of Subchondral Bone Tissue in Posttraumatic Osteoarthrosis in Rats.

In rats with modeled posttraumatic knee osteoarthrosis, negative changes in subchondral bone metabolism were revealed: a tendency to an increase in osteocalcin concentration, a decrease in sclerostin and osteoprotegerin levels, and a significant increase in FGF-23 concentration accompanied by a slight elevation of inorganic phosphorous and significant increase in total calcium levels in comparison with the corresponding parameters in intact controls. These findings demonstrate crucial importance of structural integrity of the subchondral bone, because its protection improves the results of reconstructive therapy for local cartilage defects.

Bone marrow derived mast cells injected into the osteoarthritic knee joints of mice induced by sodium monoiodoacetate enhanced spontaneous pain through activation of PAR2 and action of extracellular ATP.

Conditions that resemble osteoarthritis (OA) were produced by injection of sodium monoiodoacetate (MIA) into the knee joints of mice. Bone marrow derived mast cells (BMMCs) injected into the OA knee joints enhanced spontaneous pain. Since no spontaneous pain was observed when BMMCs were injected into the knee joints of control mice that had not been treated with MIA, BMMCs should be activated within the OA knee joints and release some pain-inducible factors. Protease activated receptor-2 (PAR2) antagonist (FSLLRY-NH2) almost abolished the pain-enhancing effects of BMMCs injected into the OA knee joints, suggesting that tryptase, a mast cell protease that is capable of activating PAR2, should be released from the injected BMMCs and enhance pain through activation of PAR2. When PAR2 agonist (SLIGKV-NH2) instead of BMMCs was injected into the OA knee joints, it was also enhanced pain. Apyrase, an ATP degrading enzyme, injected into the OA knee joints before BMMCs suppressed the pain enhanced by BMMCs. We showed that purinoceptors (P2X4 and P2X7) were expressed in BMMCs and that extracellular ATP stimulated the release of tryptase from BMMCs. These observations suggest that ATP may stimulate degranulation of BMMCs and thereby enhanced pain. BMMCs injected into the OA knee joints stimulated expression of IL-1ß, IL-6, TNF-α, CCL2, and MMP9 genes in the infrapatellar fat pads, and PAR2 antagonist suppressed the stimulatory effects of BMMCs. Our study suggests that intermittent pain frequently observed in OA knee joints may be due, at least partly, to mast cells through activation of PAR2 and action of ATP, and that intraarticular injection of BMMCs into the OA knee joints may provide a useful experimental system for investigating molecular mechanisms by which pain is induced in OA knee joints.

Human osteoclastogenesis in Epstein-Barr virus-induced erosive arthritis in humanized NOD/Shi-scid/IL-2Rγnull mice.

Many human viruses, including Epstein-Barr virus (EBV), do not infect mice, which is challenging for biomedical research. We have previously reported that EBV infection induces erosive arthritis, which histologically resembles rheumatoid arthritis, in humanized NOD/Shi-scid/IL-2Rγnull (hu-NOG) mice; however, the underlying mechanisms are not known. Osteoclast-like multinucleated cells were observed during bone erosion in this mouse model, and therefore, we aimed to determine whether the human or mouse immune system activated bone erosion and analyzed the characteristics and origin of the multinucleated cells in hu-NOG mice. Sections of the mice knee joint tissues were immunostained with anti-human antibodies against certain osteoclast markers, including cathepsin K and matrix metalloproteinase-9 (MMP-9). Multinucleated cells observed during bone erosion stained positively for human cathepsin K and MMP-9. These results indicate that human osteoclasts primarily induce erosive arthritis during EBV infections. Human osteoclast development from hematopoietic stem cells transplanted in hu-NOG mice remains unclear. To confirm their differentiation potential into human osteoclasts, we cultured bone marrow cells of EBV-infected hu-NOG mice and analyzed their characteristics. Multinucleated cells cultured from the bone marrow cells stained positive for human cathepsin K and human MMP-9, indicating that bone marrow cells of hu-NOG mice could differentiate from human osteoclast progenitor cells into human osteoclasts. These results indicate that the human immune response to EBV infection may induce human osteoclast activation and cause erosive arthritis in this mouse model. Moreover, this study is the first, to our knowledge, to demonstrate human osteoclastogenesis in humanized mice. We consider that this model is useful for studying associations of EBV infections with rheumatoid arthritis and human bone metabolism.

Associations of blood pressure and arterial stiffness with knee cartilage volume in patients with knee osteoarthritis.

OBJECTIVE: To describe the associations of blood pressure and arterial stiffness with knee cartilage volume in patients with knee OA. METHODS: A secondary analysis was performed on the data from participants in a randomized controlled trial that identified the effects of vitamin D supplementation on knee structures and symptoms among patients with symptomatic knee OA. Brachial and central blood pressure, arterial stiffness indicators and knee cartilage volume were measured at baseline and the 2 year follow-up. Associations were assessed using generalized estimating equations. RESULTS: Among 231 participants (average age 63.2 years), 48.9% were females. Higher supine systolic and diastolic pressures were significantly associated with lower tibial cartilage volume (systolic: lateral ß -6.23, medial ß -5.14, total ß -11.35 mm3/mmHg; diastolic: lateral ß -10.25, medial ß -11.29, total ß -21.50 mm3/mmHg). Higher supine systolic pressure was associated with lower femoral cartilage volume (lateral ß -17.35, total ß -28.31 mm3/mmHg). Central systolic pressure and arterial stiffness indicators (including pulse wave velocity, central pulse pressure and peripheral pulse pressure) were largely not associated with knee cartilage volume; however, higher augmentation index was associated with lower tibial and femoral cartilage volume (tibial: medial ß -8.24, total ß -19.13 mm3/%; femoral: lateral ß -23.70, medial ß -26.42, total ß -50.12 mm3/%). CONCLUSIONS: Blood pressure and arterial stiffness are associated with knee cartilage volume at several sites in knee OA patients. This supports that blood pressure and arterial stiffness may involve in the progression of knee OA.

Quantitative proteomics reveal the protective effects of EDS against osteoarthritis via attenuating inflammation and modulating immune response.

ETHNOPHARMACOLOGICAL RELEVANCE: Epimedium brevicornu Maxim, Dioscorea nipponica Makino, and Salvia miltiorrhiza Bunge formula (EDS) are three traditional Chinese medicines commonly combined and used to treat osteoarthritis (OA). However, the mechanism of its therapeutic effect on OA is still unclear. AIM OF THE STUDY: The aim of this study was to investigate the potential anti osteoarthritis mechanism of EDS in the treatment of OA rats' model by quantitative proteomics. MATERIALS AND METHODS: A papain-induced rat OA model was established, and then EDS was intragastrically administered for 28 days. A label-free quantification proteomics was performed to evaluate the holistic efficacy of EDS against OA and identify the possible protein profiles mechanisms. The expression levels of critical changed proteins were validated by RT-qPCR and Western blotting. The effects of EDS were then assessed by evaluating pathologic changes in the affected knee joint and measuring pressure pain threshold, acoustic reflex threshold, angle of joint curvature. RESULTS: Proteomics analysis showed that 62 proteins were significantly upregulated and 208 proteins were downregulated in OA group compared to control group. The changed proteins were involved in activation of humoral immunity response, complement cascade activation, leukocyte mediated immunity, acute inflammatory response, endocytosis regulation, and proteolysis regulation. The EDS treatment partially restored the protein profile changes. The protective effects of EDS on pathologic changes in OA rats' knee joint and pain threshold assessment were consisted with the proteomics results. CONCLUSIONS: The results suggest that EDS exerted synergistic therapeutic efficacies to against OA through suppressing inflammation, modulating the immune system, relieving joint pain, and attenuating cartilage degradation.

A comparative study of low-level laser efficacy on autologous activity of PRP injected in knee arthritis, in vivo study.

There were many studies that attempt to measure the effect of growth factors of platelets through platelet-rich plasma (PRP) techniques on repairing of different human tissues and their efficiency either by platelets account or measuring the concentrations of growth factors secreted from platelets at various experimental conditions, to get the optimal parameters for platelets functions in healing processes. There were little trails dealing with laser and PRP for accelerating healing process that generally takes two methods, either by studding the stimulation effect of LLLT (low-level laser therapy), by subjecting laser irradiation on injured part and left for a period of time that is necessary for photobiostimulation of cell proliferations, then PRP treatment followed, or by studding the direct effects of laser on PRP factors activity. The objectives of this study are to investigate the indirect and prolonged influence of laser irradiation (650 nm with 100 mW output power) on healing processes of knee joints with induced osteoarthritis (OA), by comparison of radiated and non-radiated PRP on repairing of joint cartilage. In material and methods, we used 9 rats divided in to four groups: C1, control without any treatment, for positive comparisons of healing; C2 and C3, controls with induced OA, left for 14 days, then sacrificed for histological analysis of negative comparisons; and P and L groups that had induced with OA for 14 days and then treated with non-irradiated and radiated PRP, respectively. Preparation of PRP (condensed platelets account with high concentration of growth factors) in order to accelerate repairing processes on induced- osteoarthritis cartilage in rats groups. To estimate the efficacy of photobiostimulation or photobioinhibition on platelets' granules, we determine the absorbance of PRP by spectrophotometer. The technique was based on PRP, as a feature of platelets quantity, that compares the quality of PRP on healing of induced osteoarthritis with and without irradiation of laser, using Wistar rats as a model. The quality of platelets was measured by time required for healing according to histopathological observations and grades of OA. Finally, the results were analyzed statistically using ANOVA test (P = 0.05). Our conclusion was emphasizing the idea of inhibiting the effect of LLLT on growth factors of PRP that is responsible of speed up healing of OA.

Fatty acid sensing GPCR (GPR84) signaling safeguards cartilage homeostasis and protects against osteoarthritis.

It is well known that free fatty acids (FFAs) have beneficial effects on the skeletal system, however, which fatty acid sensing GPCR(s) and how the GPCR(s) regulating cartilage development and osteoarthritis (OA) pathogenesis is largely unknown. In this study, we found Gpr84, a receptor for medium-chain FFAs (MCFA), was the only FFA-sensing GPCR in human and mouse chondrocytes that exhibited elevated expression when stimulated by interleukin (IL)-1ß. Gpr84-deficiency upregulated cartilage catabolic regulator expression and downregulated anabolic factor expression in the IL-1ß-induced cell model and the destabilization of the medial meniscus (DMM)-induced OA mouse model. Gpr84-/- mice exhibited an aggravated OA phenotype characterized by severe cartilage degradation, osteophyte formation and subchondral bone sclerosis. Moreover, activating Gpr84 directly enhanced cartilage extracellular matrix (ECM) generation while knockout of Gpr84 suppressed ECM-related gene expression. Especially, the agonists of GPR84 protected human OA cartilage explants against degeneration by inducing cartilage anabolic factor expression. At the molecular level, GPR84 activation inhibited IL-1ß-induced NF-κB signaling pathway. Furthermore, deletion of Gpr84 had little effect on articular and spine cartilaginous tissues during skeletal growth. Together, all of our results demonstrated that fatty acid sensing GPCR (Gpr84) signaling played a critical role in OA pathogenesis, and activation of GPR84 or MCFA supplementation has potential in preventing the pathogenesis and progression of OA without severe cartilaginous side effect.

Acupuncture reduces pain in rats with osteoarthritis by inhibiting MCP2/CCR2 signaling pathway.

Acupuncture is an emerging alternative therapy that has been beneficial for the pain of osteoarthritis (OA). However, the underlying mechanism of protective effect remains unclear. MCP1/CCR2 axis can be stimulated in various periods of OA, and we hypothesize that acupuncture may treat OA by regulating the MCP1/CCR2 axis. This study aimed to explore the effect of acupuncture at points ST35 and ST36 on the effects of hyperalgesia and cartilage in OA rats including the expression of chemokines, nerve growth factor (NGF), and inflammatory-related proteins. OA was induced in male Sprague-Dawley rats by anterior cruciate ligament transection at the right knee. The first acupuncture intervention was performed on the seventh day after surgery and once a day for seven weeks. The knee-pain-related behaviors, histology, and related protein were examined in this study. We have found that electroacupuncture at ST35 and ST36 can significantly alleviate the hyperalgesia and cartilage degeneration as well as reducing nerve sprouting in OA knee joint. Moreover, acupuncture treatment may inhibit the MCP1/CCR2 axis as well as down-regulate inflaming factor and NGF in cartilage and synovial tissue. The data presented here indicate that acupuncture exerts a protective effect against hyperalgesia and cartilage degeneration, and the mechanism might involve in chemokines and NGF pathway.

Manjarix attenuated pain and joint swelling in a rat model of monosodium iodoacetate-induced osteoarthritis.

Osteoarthritis (OA) is a joint disease characterized by degeneration of cartilage, intra-articular inflammation, remodeling of subchondral bone and joint pain. The present study was designed to assess the therapeutic effects and the possible underlying mechanism of action of Manjarix, a herbal combination composed of ginger and turmeric powder extracts, on chemically induced osteoarthritis in rats. An OA model was generated by intra-articular injection of 50 µL (40 mg mL-1) of monosodium iodoacetate (MIA) into the right knee joint of rats. After one week of osteoarthritis induction, a comparison of the anti-inflammatory efficacy of indomethacin at an oral dose of 2 mg kg-1 daily for 4 successive weeks versus five decremental dose levels of Manjarix (1000, 500, 250, 125, and 62.5 mg kg-1) was performed. Serum inflammatory cytokines, interleukin 6, interleukin 8, and tumor necrosis factor alpha; C-telopeptide of type II collagen (CTX-II) and hyaluronic acid (HA) were measured, along with weekly assessment of the knee joint swelling. Pain-like behavior was assessed and knee radiographic and histological examination were performed to understand the extent of pain due to cartilage degradation. Manjarix significantly reduced the knee joint swelling, decreased the serum levels of IL6, TNF-α, CTX-II and HA, and reduced the pathological injury in joints, with no evidence of osteo-reactivity in the radiographic examination. Manjarix also significantly prevented MIA-induced pain behavior. These results demonstrate that Manjarix exhibits chondroprotective effects and can inhibit the OA pain induced by MIA, and thus it can be used as a potential therapeutic product for OA.

Huoxuezhitong capsule ameliorates MIA-induced osteoarthritis of rats through suppressing PI3K/ Akt/ NF-κB pathway.

Huoxuezhitong capsule (HXZT, activating blood circulation and relieving pain capsule), has been applied for osteoarthritis since 1974. It consists of Angelica sinensis (Oliv.) Diels, Panax notoginseng (Burkill) F. H. Chen ex C. H., Boswellia sacra, Borneol, Eupolyphaga sinensis Walker, Pyritum. However, the direct effects of HXZT on osteoarthritis and the underlying mechanisms were poorly understood. In this study, we aimed to explore the analgesia effect of HXZT on MIA-induced osteoarthritis rat and the underlying mechanisms. The analgesia and anti-inflammatory effect of HXZT on osteoarthritis in vivo were tested by the arthritis model rats induced by monosodium iodoacetate (MIA).. Mechanistic studies confirmed that HXZT could inhibit the activation of NF-κB and down-regulate the mRNA expression of related inflammatory factors in LPS-induced RAW264.7 and ATDC5 cells. Furtherly, in LPS-induced RAW264.7 cells, HXZT could suppress NF-κB via inhibiting PI3K/Akt pathway. Taken together, HXZT capsule could ameliorate MIA-induced osteoarthritis of rats through suppressing PI3K/ Akt/ NF-κB pathway.

Cissus quadrangularis (veldt grape) attenuates disease progression and anatomical changes in mono sodium iodoacetate (MIA)-induced knee osteoarthritis in the rat model.

The Cissus quadrangularis (CQ) stem has interesting nutritional and pharmacological properties to promote the health of the skeletal system. It is a well-recognized plant in the conventional system of medicine in India for treating bone and joint-associated complications. This study focuses on identifying the active constituents from the stem and root extracts of CQ and validating its anti-osteoarthritic activity by the in vivo model. Notable levels of phenolics and flavonoids were found in the ethanol extracts of both CQ stem (CQSE) and root (CQRE), among other solvent fractions. UPLC-MS/MS analysis of these selective extracts resulted in different classes of active compounds from both positive and negative ionization modes. By analyzing their mass spectra and fragmentation pattern, 25 active compounds were identified. The CQSE and CQRE extracts, along with the standard drug (naproxen), were further tested in mono-sodium iodoacetate-induced experimental OA animals. The modulatory effects of the test extracts were assessed by haematology, synovial and cartilage marker profiling, radiology and histopathological analysis. The in vivo findings from the biochemical and physiological studies have led to the conclusion that the CQSE extract is a good choice for the management of OA. The results were substantially better than CQ root extract and naproxen drug-treated groups. Thus, CQS has bioactive constituents, which could facilitate recovery from joint tissue damage, cellular metabolism and associated risk factors attributable to dysfunctions in OA incidence and progression.

Knee arthrodesis for a congenital luxation with Larsen syndrome.

A 31-year-old woman with known Larsen syndrome presented with congenital chronic luxation of her right knee with increasing instability symptoms, which limited her daily activities. We refrained from a constrained knee arthroplasty due to her relatively young age and decided to perform a knee arthrodesis. Knee arthrodesis is a viable lifelong-lasting operative treatment alternative for specific instability-related knee disease. The knee arthrodesis was performed by double plating with an additional fixation of the patella. At 1-yearfollow-up, she was able to walk without limitations and did not experience any pain with complete consolidation of the arthrodesis. At 2-year follow-up, she performed all her daily activities without limitations. Both the Knee injury and Osteoarthritis Outcome Score (KOOS) and the International Knee Documentation Committee subjective knee form (IKDC) improved at 2-year follow-up (KOOS: 61.3; IKDC: 56.3) compared with 1-year follow-up (KOOS: 52; IKDC: 40.2).

Targeting of Phospholipase D1 Ameliorates Collagen-Induced Arthritis via Modulation of Treg and Th17 Cell Imbalance and Suppression of Osteoclastogenesis.

Phospholipase D1 (PLD1) plays a crucial role in various inflammatory and autoimmune diseases. Rheumatoid arthritis (RA) is a chronic and systemic autoimmune disease. However, the role of PLD1 in the pathogenesis of RA remains unknown. Here, we first investigated the role and effects of PLD1 in collagen-induced arthritis (CIA) and found that genetic and pharmacological inhibition of PLD1 in DBA1/J mice with CIA reduced the incidence of CIA, decreased the clinical score, and abrogated disease symptoms including infiltration of leukocytes, synovial inflammation, bone erosion, and cartilage destruction. Moreover, ablation and inhibition of PLD1 suppressed the production of type II collagen-specific IgG2a autoantibody and proinflammatory cytokines, accompanied by an increase in the regulatory T (Treg) cell population and a decrease in the Th17 cell population in CIA mice. The PLD1 inhibitor also promoted differentiation of Treg cells and suppressed differentiation of Th17 cells in vitro. Furthermore, the PLD1 inhibitor attenuated pathologic bone destruction in CIA mice by suppressing osteoclastogenesis and bone resorption. Thus, our findings indicate that the targeting of PLD1 can ameliorate CIA by modulating the imbalance of Treg and Th17 cells and suppressing osteoclastogenesis, which might be a novel strategy to treat autoimmune diseases, such as RA.

Contribution of salidroside to the relieve of symptom and sign in the early acute stage of osteoarthritis in rat model.

ETHNOPHARMACOLOGICAL RELEVANCE: The genus Rhodiola has been used to treat cough, hemoptysis, fever, pain, bruise and other symptoms which are related to injury and inflammation over a thousand years in traditional Tibetan medicine. Salidroside (p-hydroxyphenethyl-ß-D-glucoside) is one of the most potent bioactive ingredients of the genus Rhodiola. AIM OF STUDY: The present study aimed to explore whether salidroside could alleviate the clinical symptom and sign in the early acute stage of osteoarthritis (OA) in monosodium iodoacetate (MIA) rat model, and its underlying mechanisms. MATERIALS AND METHODS: Osteoarthritis (OA) was induced in rat knees by intra-articular injection of MIA; simultaneously salidroside was administered by intravenous injection. Pain behaviors were evaluated by knee-bend test, hind limb weight-bearing asymmetry and hind paw mechanical withdrawal threshold. The joint swelling was determined by the difference of knee joint diameter. Inflammatory exudates in synovial fluid were evaluated by leukocyte counting and protein content. Cytokines, chemokines, reactive oxygen species (ROS) and reactive nitrogen species (RNS) markers were determined by Enzyme-linked immunosorbent assay (ELISA) and colorimetric assay in synovial fluid. Pro-inflammatory gene expressions in synovial tissue were detected by quantitative real time RT-PCR (qRT-PCR). Nuclear factor kappa-B (NF-κB) DNA binding assay and western blot were used to determine NF-κB activation and ROS marker protein expression in synovial tissue. Glycosaminoglycan (GAG) content in the cartilage was measured by dimethylmethylene blue method. Hematoxylin and eosin (H&E), Safranin O-fast green and a modified Mankin grading system were used to evaluate the histology of articular cartilage. RESULTS: Salidroside could alleviate pain and joint swelling in the early acute stage of OA in rat model, reduced the number of leukocytes, total protein content, proinflammatory mediators and ROS/RNS markers in synovial fluid, down regulated the expression of proinflammatory genes in synovium, inhibited the activation of NF- κ B and oxidative stress response in synovium, promoted the synthesis of cartilage GAG, prevented the loss of proteoglycan and chondrocyte degeneration. CONCLUSIONS: Salidroside effectively alleviates acute symptom and sign of OA in rat model by its anti-inflammatory and antioxidant affects to inhibit synovial inflammation, which provides a new strategy to prevent the onset and progression of OA.