Antiosteoarthritic Effect of Morroniside in Chondrocyte Inflammation and Destabilization of Medial Meniscus-Induced Mouse Model.

Osteoarthritis (OA) is a common degenerative disease that results in joint inflammation as well as pain and stiffness. A previous study has reported that Cornus officinalis (CO) extract inhibits oxidant activities and oxidative stress in RAW 264.7 cells. In the present study, we isolated bioactive compound(s) by fractionating the CO extract to elucidate its antiosteoarthritic effects. A single bioactive component, morroniside, was identified as a potential candidate. The CO extract and morroniside exhibited antiosteoarthritic effects by downregulating factors associated with cartilage degradation, including cyclooxygenase-2 (Cox-2), matrix metalloproteinase 3 (Mmp-3), and matrix metalloproteinase 13 (Mmp-13), in interleukin-1 beta (IL-1ß)-induced chondrocytes. Furthermore, morroniside prevented prostaglandin E2 (PGE2) and collagenase secretion in IL-1ß-induced chondrocytes. In the destabilization of the medial meniscus (DMM)-induced mouse osteoarthritic model, morroniside administration attenuated cartilage destruction by decreasing expression of inflammatory mediators, such as Cox-2, Mmp3, and Mmp13, in the articular cartilage. Transverse microcomputed tomography analysis revealed that morroniside reduced DMM-induced sclerosis in the subchondral bone plate. These findings suggest that morroniside may be a potential protective bioactive compound against OA pathogenesis.

Loganin ameliorates cartilage degeneration and osteoarthritis development in an osteoarthritis mouse model through inhibition of NF-κB activity and pyroptosis in chondrocytes.

ETHNOPHARMACOLOGICAL RELEVANCE: Corni Fructus (CF), the red fruit of Cornus officinalis Siebold & Zucc, has been used both as food and medicinal herb in traditional Chinese medicine (TCM). Loganin is a major iridoid glycoside and one of the quality control indexes of CF. In TCM clinical practice, prescription containing CF is commonly used to treat osteoarthritis (OA), but the underlying mechanisms of loganin are not yet utterly understood. AIM OF THE STUDY: The aims of the present study are to confirm the therapeutic effects of loganin in an OA mouse model and to determine the mechanisms involved in the OA protective effects. MATERIALS AND METHODS: The destabilization of the medial meniscus (DMM) procedure was performed on the right knee of 8-week-old C57BL/6 male mice. 30 or 100 µg/ml of loganin was then injected into articular space twice a week for 8 and 12-week. Safranin O/Fast green staining, H&E staining, micro-CT analysis were performed to analyze structural and morphological changes. The protein expression of collagen type II (Col2), metalloproteinase-3 (Mmp3), matrix metalloproteinase 13 (Mmp13) collagen type X (Col10), cryopyrin and caspase-1 were detected by immunochemistry staining. Immuno-fluorescence assay was performed to assess changes in expression of CD31, endomucin, p65 and p-I-κB. RESULTS: Results of histomorphometry showed that loganin delays the progression of OA in the DMM model. In cartilage, loganin decreased the OARSI score, increasing hyaline cartilage (HC) thickness and decreasing calcified cartilage (CC) thickness. Moreover, loganin inhibited osteophyte formation, reduced the bone volume fraction (BV/TV), lowered trabecular thickness (Tb.Th) and increased trabecular separation (Tb.Sp) in subchondral bone. Mechanistically, loganin increased the expressions of Col2, decreases the expression of Mmp3, Mmp13, Col10, cryopyrin and caspase-1 in cartilage. In parallel, loganin inhibited the expression of CD31 and endomucin in subchondral bone. Furthermore, loganin suppressed nuclear translocation of p65 protein, and decreased the amount of p-I-κB in chondrocytes. CONCLUSIONS: In summary, these results uncovered that loganin inhibits NF-κB signaling and attenuates cartilage matrix catabolism and pyroptosis of chondrocytes in articular cartilage. Loganin may serve as a potential therapeutic agent for OA treatment.

Bushenhuoxue formula attenuates cartilage degeneration in an osteoarthritic mouse model through TGF-ß/MMP13 signaling.

BACKGROUND: Articular cartilage degeneration plays a key role in the pathogenesis of osteoarthritis (OA). Bushenhuoxue formula (BSHXF) has been widely used in the treatment of OA in clinics. However, the molecular mechanisms responsible for the chondroprotective effect of BSHXF remain to be elucidated. The purpose of this study was to explore the effects of BSHXF on OA mice model. METHODS: In this study, we investigated the effects of BSHXF on destabilization of the medial meniscus (DMM)-induced chondrocyte degradation in OA mice model. At 12 weeks post-surgery, the joints were harvested for tissue analyses, including histology, histomorphometry, TUNEL, OARSI scoring, micro-CT and immunohistochemistry for COL2, TGFBR2, pSMAD2 and MMP13. Additionally, we also evaluated the effects of BSHXF on Mmp13 mRNA and protein expression in chondrogenic ATDC5 cells through real-time PCR and Western blot respectively. Moreover, we investigated the chondroprotective effect of BSHXF on mice with Tgfbr2 conditional knockout (Tgfbr2 Col2ER mice) in chondrocyte, including the relative experiments mentioned above. We transfected Tgfbr2 siRNA in ATDC5 to further evaluate the changes of Mmp13 mRNA and protein expression followed by BSHXF treatment. RESULTS: Amelioration of cartilage degradation and chondrocyte apoptosis were observed in DMM-induced mice, with increases in cartilage area and thickness, proteoglycan matrix, COL2 content and decreases in OARSI score at 12 weeks post surgery. Moreover, the elevated TGFBR2 and pSMAD2, and reduced MMP13 positive cells were also revealed in DMM-induced mice treated with BSHXF. Besides, decreased Mmp13 mRNA and protein expression were observed inchondrogenic ATDC5 cells culture in serum containing BSHXF. As expected, Tgfbr2 Col2ER mice exhibited significant OA-like phenotype. Interestingly, obvious improvement in articular cartilage structure was still observed in Tgfbr2 Col2ER mice after BSHXF treatment via up-regulated pSMAD2 and down-regulated MMP13 expressional levels in articular cartilage. CONCLUSIONS: BSHXF could inhibit cartilage degradation through TGF-ß/MMP13 signaling, and be considered a good option for the treatment of OA.

Prediction Models to Improve the Diagnostic Value of Plain Radiographs in Children With Complete Discoid Lateral Meniscus.

PURPOSE: To develop prediction models to improve the diagnostic utility of plain radiographs for the diagnosis of complete discoid lateral meniscus by combining previously reported radiographic findings. METHODS: Patients ages 5 to 16 years with complete discoid lateral meniscus confirmed by arthroscopy or magnetic resonance imaging were included. Patients with insufficient radiographs were excluded. Normal control subjects were randomly sampled by age and sex matching. Subjects were divided into 2 groups considering skeletal maturation (5-9 and 10-16 years). Radiographic variables included were lateral joint space, height of the fibular head, height of the lateral tibial spine, obliquity and cupping of the lateral tibial plateau, condylar cutoff sign, and squaring and notching of the lateral femoral condyle. Prediction models were developed by regression analyses. The cutoff value (COV) for best accuracy was determined with its sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). RESULTS: A total of 162 knees (126 patients) with complete discoid lateral meniscus and 151 age- and sex-matched knees (151 subjects) with normal meniscus were included. In subjects 5 to 9 years old, the prediction model was risk score = [-20.08 * height of the fibular head/femoral interepicondylar distance (FIED)] + [-42.26 * height of the lateral tibial spine/FIED]. The COV of -8.47 showed the best accuracy (74.4%), with sensitivity of 85.9%; specificity, 60.4%; PPV, 72.4%; and NPV, 78.0%. In subjects 10 to 16 years old, the prediction model was risk score = [77.04 * lateral joint space/FIED] + [-34.55 * height of the fibular head/FIED] + [-56.58 * height of the lateral tibial spine/FIED] + [-16.44 * condylar cutoff sign]. The COV of -18.03 showed the best accuracy (85.4%), with sensitivity of 79.6%; specificity, 90.4%; PPV, 87.6%; and NPV, 83.9%. CONCLUSIONS: The prediction models combining the plain radiographic findings showed higher diagnostic values than the diagnostic values of the individual radiographic findings. The results of this study provide improved diagnostic utility of plain radiography for the detection of completed discoid lateral meniscus in children. LEVEL OF EVIDENCE: Level III, diagnostic study.

Paeonol alleviates interleukin-1ß-induced inflammatory responses in chondrocytes during osteoarthritis.

Interleukin-1ß (IL-1ß)-induced inflammatory responses in chondrocytes play an important role in the pathogenesis of osteoarthritis (OA). Searching medicines that affect IL-1ß-mediated chondrocytes function is critical in developing therapies for OA. Paeonol, as an important component in traditional Chinese medicine, has anti-inflammatory activity and can offer therapy for a multitude of inflammatory-related diseases. The purpose of this study was to investigate whether paeonol could alleviate the progression of OA through inhibition of IL-1ß-induced inflammatory responses in chondrocytes. The cell counting kit-8 assay, 5-ethynil-2'-deoxyuridine staining, hoechst 33258 staining and flow cytometric staining were used to observe the chondrocytes proliferation and apoptosis. Western blot and quantitative real-time PCR were applied to examine the expression of extracellular matrix and cartilage degrading enzymes. Reactive oxygen species (ROS) production was monitored by 2',7'-dichlorodihydrofluoresce in diacetate staining. Furthermore, paeonol was intra-articularly injected into joint capsule in destabilized medial meniscus (DMM)-induced OA rat model for 8 and 12 weeks. The results showed that paeonol could negatively affect IL-1ß-mediate chondrocyte apoptosis and proliferation. Application of paeonol attenuated the secretion of cartilage extracellular matrix and cartilage degrading enzymes induced by IL-1ß in chondrocytes. Increasing of ROS production by IL-1ß was obviously alleviated by paeonol. Besides, paeonol alleviated DMM-induced articular cartilage degeneration in vivo. Taken together, we concluded that paeonol might be used as therapeutic agent for treating OA.

Serum and synovial fluid lipidomic profiles predict obesity-associated osteoarthritis, synovitis, and wound repair.

High-fat diet-induced obesity is a major risk factor for osteoarthritis (OA) and diminished wound healing. The objective of this study was to determine the associations among serum and synovial fluid lipid levels with OA, synovitis, adipokine levels, and wound healing in a pre-clinical obese mouse model of OA. Male C57BL/6 J mice were fed either a low-fat (10% kcal) or one of three high-fat (HF, 60% kcal) diets rich in saturated fatty acids (SFAs), ω-6 or ω-3 polyunsaturated FAs (PUFAs). OA was induced by destabilization of the medial meniscus. Mice also received an ear punch for evaluating wound healing. Serum and synovial fluid were collected for lipidomic and adipokine analyses. We demonstrated that the serum levels of ω-3 PUFAs were negatively correlated with OA and wound size, but positively correlated with adiponectin levels. In contrast, most ω-6 PUFAs exhibited positive correlations with OA, impaired healing, and inflammatory adipokines. Interestingly, levels of pentadecylic acid (C15:0, an odd-chain SFA) and palmitoleic acid were inversely correlated with joint degradation. This study extends our understanding of the links of FAs with OA, synovitis and wound healing, and reports newly identified serum and synovial fluid FAs as predictive biomarkers of OA in obesity.

Nerve growth factor inhibition with tanezumab influences weight-bearing and subsequent cartilage damage in the rat medial meniscal tear model.

OBJECTIVE: To investigate whether the effects of nerve growth factor (NGF) inhibition with tanezumab on rats with medial meniscal tear (MMT) effectively model rapidly progressive osteoarthritis (RPOA) observed in clinical trials. METHODS: Male Lewis rats underwent MMT surgery and were treated weekly with tanezumab (0.1, 1 or 10 mg/kg), isotype control or vehicle for 7, 14 or 28 days. Gait deficiency was measured to assess weight-bearing on the operated limb. Joint damage was assessed via histopathology. A second arm, delayed onset of treatment (starting 3-8 weeks after MMT surgery) was used to control for analgesia early in the disease process. A third arm, mid-tibial amputation, evaluated the dependency of the model on weight-bearing. RESULTS: Gait deficiency in untreated rats was present 3-7 days after MMT surgery, with a return to normal weight-bearing by days 14-28. Prophylactic treatment with tanezumab prevented gait deficiency and resulted in more severe cartilage damage. When onset of treatment with tanezumab was delayed to 3-8 weeks after MMT surgery, there was no increase in cartilage damage. Mid-tibial amputation completely prevented cartilage damage in untreated MMT rats. CONCLUSIONS: These data suggest that analgesia due to NGF inhibition during the acute injury phase is responsible for increased voluntary weight-bearing and subsequent cartilage damage in the rat MMT model. This model failed to replicate the hypotrophic bone response observed in tanezumab-treated patients with RPOA.

Do the radiographic findings of symptomatic discoid lateral meniscus in children differ from normal control subjects?

PURPOSE: The aim of this study was to quantitatively compare radiographic findings of symptomatic discoid lateral meniscus in children with those of matched controls. METHODS: Seventy-eight consecutive children (91 knees) who underwent arthroscopic surgery for a symptomatic discoid lateral meniscus (discoid group) were included. Another 91 age- and sex-matched controls with normal medial and lateral menisci on the basis of magnetic resonance imaging findings were included in this study (control group). Each plain radiograph was evaluated from the anteroposterior view for the following variables: height of the lateral tibial spine, lateral joint space distance, height of the fibular head, squaring of the lateral femoral condyle, obliquity of the lateral tibial plateau and cupping of the lateral tibial plateau. Lateral femoral condylar notch was evaluated in lateral view. Statistical analyses were used to determine the differences between the two groups. RESULTS: A significant difference in the mean height of the lateral tibial spine, lateral joint space distance, height of the fibular head, and obliquity of the lateral tibial plateau distinguished the two groups (p < 0.0001). However, there was no statistical difference in the condylar off sign, squaring of the lateral femoral condyle, cupping of the lateral tibial plateau and lateral femoral condylar notch between groups (n.s.). The cut-off values for the height of the lateral tibial spine (6 mm), lateral joint space distance (8 mm), height of the fibular head (14.9 mm) and obliquity of the lateral tibial plateau (17.6°) were determined. With these cut-off values in diagnosing discoid lateral meniscus, the sensitivity and accuracy of height of the fibular head were 78 and 70 %, respectively. CONCLUSIONS: Several plain radiographic findings in symptomatic discoid lateral meniscus in children were significantly different from those in normal control. These findings would be helpful in screening tool of discoid lateral meniscus for children. LEVEL OF EVIDENCE: II.

Melanocortin 1 receptor-signaling deficiency results in an articular cartilage phenotype and accelerates pathogenesis of surgically induced murine osteoarthritis.

Proopiomelanocortin-derived peptides exert pleiotropic effects via binding to melanocortin receptors (MCR). MCR-subtypes have been detected in cartilage and bone and mediate an increasing number of effects in diathrodial joints. This study aims to determine the role of MC1-receptors (MC1) in joint physiology and pathogenesis of osteoarthritis (OA) using MC1-signaling deficient mice (Mc1re/e). OA was surgically induced in Mc1re/e and wild-type (WT) mice by transection of the medial meniscotibial ligament. Histomorphometry of Safranin O stained articular cartilage was performed with non-operated controls (11 weeks and 6 months) and 4/8 weeks past surgery. µCT-analysis for assessing epiphyseal bone architecture was performed as a longitudinal study at 4/8 weeks after OA-induction. Collagen II, ICAM-1 and MC1 expression was analysed by immunohistochemistry. Mc1re/e mice display less Safranin O and collagen II stained articular cartilage area compared to WT prior to OA-induction without signs of spontaneous cartilage surface erosion. This MC1-signaling deficiency related cartilage phenotype persisted in 6 month animals. At 4/8 weeks after OA-induction cartilage erosions were increased in Mc1re/e knees paralleled by weaker collagen II staining. Prior to OA-induction, Mc1re/e mice do not differ from WT with respect to bone parameters. During OA, Mc1re/e mice developed more osteophytes and had higher epiphyseal bone density and mass. Trabecular thickness was increased while concomitantly trabecular separation was decreased in Mc1re/e mice. Numbers of ICAM-positive chondrocytes were equal in non-operated 11 weeks Mc1re/e and WT whereas number of positive chondrocytes decreased during OA-progression. Unchallenged Mc1re/e mice display smaller articular cartilage covered area without OA-related surface erosions indicating that MC1-signaling is critical for proper cartilage matrix integrity and formation. When challenged with OA, Mc1re/e mice develop a more severe OA-pathology. Our data suggest that MC1-signaling protects against cartilage degradation and subchondral bone sclerosis in OA indicating a beneficial role of the POMC system in joint pathophysiology.

Treatment with SiMiaoFang, an anti-arthritis chinese herbal formula, inhibits cartilage matrix degradation in osteoarthritis rat model.

A Chinese herbal preparation, SiMiaoFang (SMF), has been used clinically for treating arthralgia by virtue of its anti-inflammatory and pain-relieving activities. However, no evidence base links SMF to anti-osteoarthritis (OA), particularly its link to inhibiting cartilage matrix degradation. In this study, we undertook a characterization of anti-OA activity of SMF using an in vivo rat model induced by anterior cruciate ligament transection and medial meniscus resection (ACLT+MMx) together with in vitro studies with chondrocytes for further molecular characterization. ACLT+MMx rats were treated with SMF at doses of 0.63, 1.25, and 2.5 grams/kg per day for 6 weeks. SMF treatments significantly inhibited cartilage matrix degradation, as indicated by increasing proteoglycan and collagen content, particularly type II collagen expression in articular cartilage, decreasing CTX-II (collagen type II degradation marker), and increasing CPII (collagen type II synthesis marker) in circulation. Moreover, SMF suppressed synovial inflammation and inhibited release of interleukin-1ß (IL-1ß) and tumor necrosis factor-α in serum. The levels of serum prostaglandin E2 and nitric oxide productions were decreased via suppression of the production of cyclooxygenase-2 and inducible nitric oxide synthase, respectively. Importantly, SMF interfered with OA-augmented expression of matrix metalloproteinases (MMPs) -3 and -13 and aggrecanases (ADAMTS) -4 and -5, which are considered to be key enzymes in cartilage matrix degradation, and simultaneously augmented OA-reduced tissue inhibitors of metalloproteinases (TIMPs) -1 and -3 expression in the joints. The largest changes in these parameters were found at the highest dose. Meanwhile, SMF significantly decreased MMP-3 and -13 and increased TIMP-1 and -3 at mRNA and protein levels in IL-1ß-induced chondrocytes. These findings provide the first evidence that SMF effectively treats OA by inhibiting cartilage matrix degradation.

Strontium ranelate reduces cartilage degeneration and subchondral bone remodeling in rat osteoarthritis model.

AIM: To investigate whether strontium ranelate (SR), a new antiosteoporotic agent, could attenuate cartilage degeneration and subchondral bone remodeling in osteoarthritis (OA). METHODS: Medial meniscal tear (MMT) operation was performed in adult SD rats to induce OA. SR (625 or 1800 mg·kg(-1)·d(-1)) was administered via gavage for 3 or 6 weeks. After the animals were sacrificed, articular cartilage degeneration was evaluated using toluidine blue O staining, SOX9 immunohistochemistry and TUNEL assay. The changes in microarchitecture indices and tissue mineral density (TMD), chemical composition (mineral-to-collagen ratio), and intrinsic mechanical properties of the subchondral bones were measured using micro-CT scanning, confocal Raman microspectroscopy and nanoindentation testing, respectively. RESULTS: The high-dose SR significantly attenuated cartilage matrix and chondrocyte loss at 6 weeks, and decreased chondrocyte apoptosis, improved the expression of SOX9, a critical transcription factor responsible for the expression of anabolic genes type II collagen and aggrecan, at both 3 and 6 weeks. Meanwhile, the high-dose SR also significantly attenuated the subchondral bone remodeling at both 3 and 6 weeks, as shown by the improved microarchitecture indices, TMD, mineral-to-collagen ratio and intrinsic mechanical properties. In contrast, the low-dose SR did not significantly change all the detection indices of cartilage and bone at both 3 and 6 weeks. CONCLUSION: The high-dose SR treatment can reduce articular cartilage degeneration and subchondral bone remodeling in the rat MMT model of OA.

Low-level laser therapy in meniscal pathology: a double-blinded placebo-controlled trial.

We performed a randomized, double-blinded, placebo-controlled study (ISRCTN24203769) to assess the effectiveness of low-level laser therapy (LLLT) in patients with meniscal pathology, including only symptomatic patients with tiny focus of grade 3 attenuation (seen only on 0.7 thickness sequences) or intrasubstance tears with spot of grade 3 signal intensity approaching the articular surface. None of the patients in the study group underwent arthroscopy or new magnetic resonance imaging investigation. Paired-samples t test was used to detect significant changes in subjective knee pain over the experimental period within groups, and ANOVA was used to detect any significant differences between the two groups. Pain was significantly improved for the LLLT group than for the placebo group (F = 154, p < 0.0001). Pain scores were significantly better after LLLT. Four (12.5 %) patients did not respond to LLLT. At baseline, the average Lysholm score was 77 ± 4.6 for the LLLT group and 77.2 ± 2.6 for the placebo group (p > 0.05). Four weeks after LLLT or placebo therapy, the laser group reported an average Lysholm score of 82.5 ± 4.6, and the placebo group scored 79.0 ± 1.9. At 6 months, the laser group had an average Lysholm score of 82.2 ± 5.7, and after 1 year, they scored 81.6 ± 6.6 (F = 14.82923, p = 0.002). Treatment with LLLT was associated with a significant decrease of symptoms compared to the placebo group: it should be considered in patients with meniscal tears who do not wish to undergo surgery.

Medical exercise therapy, and not arthroscopic surgery, resulted in decreased depression and anxiety in patients with degenerative meniscus injury.

The purpose of this pilot study was to compare the effectiveness of conservative therapy involving medical exercise therapy (MET) versus arthroscopic surgery in patients with knee pain, with MRI-verified degenerative meniscus. The patients were randomly assigned either to MET (n = 9) or to arthroscopic surgery (n = 8). Patients receiving MET had 3 treatments a week for 3 months, a total of 36 treatments. The arthroscopy consisted of meniscectomy with no structured conservative therapy after surgery. Assessment of pain, function, anxiety and depression were performed at inclusion and after 3 months. At the end of treatment, which was 3 months after inclusion, there were no statistical differences between the two groups regarding pain and function. However, anxiety and depression were significantly reduced in the MET group compared with the patients receiving arthroscopic surgery. Bearing in mind the low number of included patients in this pilot study, arthroscopy was found to be no better than MET regarding knee pain and overall daily function. The results from this pilot study are similar to other clinical studies, thereby demonstrating that conservative therapy is just as effective as surgery.

Regulation of osteoarthritis by omega-3 (n-3) polyunsaturated fatty acids in a naturally occurring model of disease.

OBJECTIVE: To examine effects of high omega-3 (n-3) polyunsaturated fatty acid (PUFA) diets on development of osteoarthritis (OA) in a spontaneous guinea pig model, and to further characterise pathogenesis in this model. Modern diets low in n-3 PUFAs have been linked with increases in inflammatory disorders, possibly including OA. However, n-3 is also thought to increases bone density, which is a possible contributing factor in OA. Therefore we aim to determine the net influence of n-3 in disease development. METHOD: OA-prone Dunkin-Hartley (DH) Guinea pigs were compared with OA-resistant Bristol Strain-2s (BS2) each fed a standard or an n-3 diet from 10 to 30 weeks (10/group). We examined cartilage and subchondral bone pathology by histology, and biochemistry, including collagen cross-links, matrix metalloproteinases (MMPs), alkaline phosphatase, glycosaminoglycan (GAG), and denatured type II collagen. RESULTS: Dietary n-3 reduced disease in OA-prone animals. Most cartilage parameters were modified by n-3 diet towards those seen in the non-pathological BS2 strain - significantly active MMP-2, lysyl-pyridinoline and total collagen cross-links - the only exception being pro MMP-9 which was lower in the BS2, yet increased with n-3. GAG content was higher and denatured type II lower in the n-3 group. Subchondral bone parameters in the DH n-3 group also changed towards those seen in the non-pathological strain, significantly calcium:phosphate ratios and epiphyseal bone density. CONCLUSION: Dietary n-3 PUFA reduced OA in the prone strain, and most disease markers were modified towards those of the non-OA strain, though not all significantly so. Omega-3 did not increase markers of pathology in either strain.

Synovial colony-stimulating factor-1 mRNA expression in diffuse pigmented villonodular synovitis.

OBJECTIVES: To delineate the molecular mechanisms underlying the process of the diffuse-type giant cell tumours, also called pigmented villonodular synovitis, a rare, aggressive condition of the synovium, the knee synovial tissue expression of colony-stimulating factor-1 gene, as detected by real-time polymerase chain reaction, was compared between patients affected with pigmented villonodular knee synovitis and knee meniscal tears, or persistent gonoarthitis. METHODS: Multiple synovial biopsies of the knee were performed by arthroscopy in five consecutive patients affected by diffuse pigmented villonodular knee synovitis and in 12 patients affected by knee meniscal tears (n. 6) or persistent active gonarthritis (n. 6), recruited from the patients attending the Rheumatology Day Surgery Outpatient Clinic of the University of Padova Hospital. The ethics committee approved the study protocol and the participants signed consent statements after being informed about the content of the study. The diagnosis was made on the basis of a histological examination. The colony-stimulating factor-1 gene expression was assessed by reverse transcription followed by real-time polymerase chain reaction. RESULTS: The detection by RT-PCR of synovial colony-stimulating factor-1 mRNA showed a wide spectrum of expression in the three groups of distinct knee joint disease affected patients, with significantly higher level of colony-stimulating factor-1 mRNA expression in synovial tissue of pigmented villonodular synovitis, in comparison to that of knee meniscal injuries and persistent gonoarthritis patients. CONCLUSIONS: Our findings point out to an important role of colony-stimulating factor-1 in pigmented villonodular knee synovitis disease process and support the idea that colony-stimulating factor-1/colony-stimulating factor-1 receptor interaction may represent a potential therapeutic target of this disease.

Postoperative pain management and acupuncture: a case report of meniscal cyst excision.

We report a case of pain management after a meniscal cyst excision, with the use of electroacupuncture (EA). There are a few reports which indicate that postoperative pain management is prerequisite for the patient's optimal recovery, but surveys in the UK and the USA have identified an unacceptable prevalence of poor pain control after surgery, which might increase the risk of a chronic pain state. The conventional treatment of postoperative pain includes systemic medications such as opioids, non-steroidal anti-inflammatory drugs and other non-opioid agents. In our case, the rehabilitation lasted for 6 months without significant benefit. After that period our patient was treated with EA. By the end of the first EA session the relief of pain was notable and after a course of 10 treatments the patient reported complete relief of the symptoms with no recurrence during a 2 year follow up period. In conclusion, this might indicate that EA could be useful for postoperative pain management.

4 T MRI of chondrocalcinosis in combination with three-dimensional CT, radiography, and arthroscopy: a report of three cases.

OBJECTIVE: To describe 4 T MRI techniques in imaging chondrocalcinosis within the knee and examine the results together with those demonstrated using three-dimensional (3D) computed tomography, conventional radiography, and arthroscopy. DESIGN AND PATIENTS: From a larger clinical imaging study of early osteoarthritis, knee arthroscopy patients were imaged using high-field MRI and high-resolution 3D CT prior to their surgery. Retrospective review of the imaging data diagnosed three patients with chondrocalcinosis. Fat-suppressed 3D spoiled gradient (3D SPGR) and two-dimensional fat-suppressed fast spin echo (FSE) imaging was performed at 4 T. The MR images, multi-planar reformatted CT (MPR-CT) and maximum intensity projection CT (MIP-CT) images, and radiographs were examined by a musculoskeletal radiologist for the presence and location of chondrocalcinosis. The findings from arthroscopy were also included. RESULTS: MRI showed 16 sites of punctate hypointense regions from 18 articular surfaces and five of six menisci with similar signal characteristics. Both meniscal chondrocalcinosis and meniscal tears were clearly visible using the 3D SPGR sequence. Only three sites were demonstrated to have calcification using MPR-CT and MIP-CT revealed an additional three. In articular cartilage surfaces showing surface disruption, arthroscopy demonstrated 11 sites with crystal deposition. Arthroscopy also revealed five menisci with calcification present. CONCLUSION: Our preliminary findings suggest that imaging chondrocalcinosis using spoiled gradient 4 T MRI is superior and complementary to the other imaging modalities in the detection of crystal deposition in both articular cartilage and menisci.

Relationship between meniscal degeneration and element contents.

The purpose of this study is to investigate the relationship between meniscal degeneration and element contents. The contents of elements (calcium, phosphorus, sulfur, and magnesium) in the menisci from 17 patients with osteoarthritis (OA) of the knee, 6 with rheumatoid arthritis (RA), and 2 who underwent the surgical operation for malignant tumors (control) were analyzed by inductively coupled plasma-atomic emission spectrometry, and the menisci were divided into four stages (Stage 0-3) of histological degeneration. The calcium contents of the menisci were 0.26 +/- 0.16 in Stage 0, 0.50 +/- 0.37 in Stage 1, and 0.69 +/- 0.66 in Stage 2, respectively (the values represent mg elements/g dry tissue). They increased with the progression of the stage. This tendency was found in the menisci with OA, but was not clear in those with RA. The calcium content in the control group was 0.17 +/- 0.09 mg/g. There was no significant relationship between the stage of degeneration and the contents of phosphorus, sulfur, or magnesium. The calcium content of the meniscus might indicate the degree of meniscal degeneration.

Radiographic knee dimensions in discoid lateral meniscus: comparison with normal control.

We reviewed the knee radiographs of 68 cases of arthroscopically proven discoid lateral meniscus, including 42 cases of complete type and 26 cases of incomplete type discoid lateral meniscus. Knee radiographs of 70 cases that had no arthroscopic evidence of pathology of the meniscus were used as controls. We excluded patients who had significant trauma history and who were under 16 years of age or over 60 years to avoid measuring radiographs of skeletally immature or degenerative knees. The absolute values and relative normalized values of specific knee dimensions, such as a squared-off appearance of the lateral femoral condyle, widened femorotibial joint space, cupping of the lateral tibial plateau, obliquity of the lateral tibial plateau articular surface, high fibular head, and hypoplasia of the lateral intercondylar spine, were compared between the patients with discoid lateral meniscus and the normal controls. Among those dimensions, high fibular head and widened lateral tibiofemoral joint space showed statistically significant differences between the discoid lateral meniscus group and normal control group. We suggest that these findings would be useful in screening lateral discoid meniscus on plain radiography.

Development of artificial articular cartilage.

Attempts have been made to develop an artificial articular cartilage on the basis of a new viewpoint of joint biomechanics in which the lubrication and load-bearing mechanisms of natural and artificial joints are compared. Polyvinyl alcohol hydrogel (PVA-H), 'a rubber-like gel', was investigated as an artificial articular cartilage and the mechanical properties of this gel were improved through a new synthetic process. In this article the biocompatibility and various mechanical properties of the new improved PVA-H is reported from the perspective of its usefulness as an artificial articular cartilage. As regards lubrication, the changes in thickness and fluid pressure of the gap formed between a glass plate and the specimen under loading were measured and it was found that PVA-H had a thicker fluid film under higher pressures than polyethylene (PE) did. The momentary stress transmitted through the specimen revealed that PVA-H had a lower peak stress and a longer duration of sustained stress than PE, suggesting a better damping effect. The wear factor of PVA-H was approximately five times that of PE. Histological studies of the articular cartilage and synovial membranes around PVA-H implanted for 8-52 weeks showed neither inflammation nor degenerative changes. The artificial articular cartilage made from PVA-H could be attached to the underlying bone using a composite osteochondral device made from titanium fibre mesh. In the second phase of this work, the damage to the tibial articular surface after replacement of the femoral surface in dogs was studied. Pairs of implants made of alumina, titanium or PVA-H on titanium fibre mesh were inserted into the femoral condyles. The two hard materials caused marked pathological changes in the articular cartilage and menisci, but the hydrogel composite replacement caused minimal damage. The composite osteochondral device became rapidly attached to host bone by ingrowth into the supporting mesh. The clinical implications of the possible use of this material in articular resurfacing and joint replacement are discussed.