Chondrotoxicity of Liposomal Bupivacaine in Articular Chondrocytes: Preliminary Findings.

OBJECTIVE: The chondrotoxicity of local anesthetics has been previously recognized. Recent introduction of a liposomal formulation of bupivacaine has been found to significantly improve postoperative pain control but its effect on chondrocyte viability has yet to be investigated with this new formulation. We sought to assess the in vitro chondrotoxicity of liposomal bupivacaine. METHODS: Chondrocytes were isolated from articular cartilage from fresh stifle joints and grown in culture medium. Cultured chondrocyte-derived cells (CDCs) were treated with 0.9% normal saline solution, 0.5%, 0.25%, and 0.13% bupivacaine and ropivacaine, 1.3% liposomal bupivacaine for 1 hour. Following treatment, cells were washed and incubated in media for 23 hours. The CDCs were then harvested and viability was assessed by flow cytometry using SYTOX green dead cell stain. RESULTS: Treated CDCs demonstrated a dose-response effect for chondrocyte viability when treated with bupivacaine, ropivacaine, and liposomal bupivacaine. Liposomal bupivacaine demonstrated the highest chondrocyte viability following treatment. Ropivacaine demonstrated higher chondrocyte viability than bupivacaine. CONCLUSION: Following 1 hour of treatment, liposomal bupivacaine demonstrated the highest chondrocyte viability. Chondrocyte viability was inversely proportional to anesthetic concentration.

Preventive administration of juanbi capsules for knee osteoarthritis: effects on serum MMP-2 and MMP-9 levels and cartilage repair.

OBJECTIVE: To explore the mechanism of action of Juanbi Capsules, a Chinese medicine for invigorating the kidney and replenishing qi, in preventing osteoarthritis of the knee in rabbits. METHODS: Seventy-two 4-month-old, Japanese long-eared white rabbits were randomly divided into 6 groups: control (group A), model (group B), Chinese drug; high-dose (group C), Chinese drug; mid-dose (group D), Chinese drug; low-dose (group E), and drug control (group F). With the exception of the rabbits in group A, each rabbit was subjected to plaster cast fixation for 6 weeks to induce osteoarthritis. In addition, rabbits were administrated with an intragastric injection of the Chinese drug (groups C, D and E) or an aminoglucose hydrochloride capsule (group F) for 4 weeks. Blood was drawn from the central ear artery for serum MMP-2 and MMP-9 concentrations, and the knee joint cartilage was harvested for gross observation and light microscopy. RESULTS: There were significant differences in serum MMP-2 and MMP-9 concentrations between group B and groups C, D and E (P < 0.05), with no significant differences between groups D and F. Histological results showed various changes in tissue staining with treatment, with osteophyte and bone cyst formation, and superficial erosion in the articular surface of the cartilage; in some cases, the defect reached the mid-layer of the cartilage, and these changes were lower than those in the model group. CONCLUSION: Juanbi Capsules assist in preventing osteoarthritis in the rabbit, possibly by decreasing serum MMP-2 and MMP-9 levels.

Mechanisms of impaired growth: effect of steroids on bone and cartilage.

BACKGROUND: Long-term treatment with high-dose glucocorticoids (GCs) has profound effects on bone metabolism and linear growth. Bone metabolism is a balance between bone resorption by osteoclasts and new bone formation by osteoblasts. Systemically, GC treatment reduces circulating levels of estrogen and modestly increases parathyroid hormone levels. At the local level, GCs decrease insulin-like growth factor I (IGF-I) production, induce IGF-I resistance and increase nuclear factor kappaB ligand production by osteoblasts. These alterations inhibit new bone formation and stimulate bone resorption, with a net loss of bone over time. Clinically, this results in decreased bone mineral density, osteoporosis and increased risk for fracture. Local effects of GCs at the growth plate include reduction of IGF-I production, inducing IGF-I resistance and reducing production of C-type natriuretic peptide, which results in a reduction of chondrocyte proliferation, matrix synthesis and hypertrophy. These reductions in chondrocyte function result in decreased linear growth. CONCLUSIONS: The effects of GCs on bone metabolism and linear growth are sensitive and specific and represent an evolutionary adaptation to redirect resources during times of physiologic stress. Since many of these effects result from alterations in IGF-I production, growth hormone therapy is a potential approach to ameliorate these problems.

Diabetes and rheumatic diseases.

PURPOSE OF REVIEW: This review summarizes recent advances in the field of diabetes and rheumatic disease. These conditions exert a significant healthcare burden on our society and much remains to be learned regarding their pathophysiology and treatment. RECENT FINDINGS: We summarize new insights into diabetes and its association with osteoarthritis, rheumatoid arthritis, carpal tunnel syndrome, osteoporosis, diffuse idiopathic skeletal hyperostosis, crystalline arthropathy, neuropathic arthropathy, and tendinopathy. Diabetes has major effects on connective tissues, which have significant impact on both the development and outcome of these diseases of cartilage, bone, ligament, and tendon. An improved understanding of the mechanisms through which diabetes alters connective tissue metabolism should lead to better preventive and therapeutic interventions. SUMMARY: Incremental progress has been made in understanding the interactions between diabetes and common musculoskeletal syndromes. Although this review highlights exciting areas of future interest, more work in this field is certainly warranted.

Protective effect of Withania somnifera root powder in relation to lipid peroxidation, antioxidant status, glycoproteins and bone collagen on adjuvant-induced arthritis in rats.

The present investigation was carried out to evaluate the protective effect of Withania somnifera Linn. Dunal (family-Solanaceae), commonly known as Ashwagandha, on adjuvant-induced arthritic rats. Results were compared with those for Indomethacin, a nonsteroidal anti-inflammatory drug. Arthritis was induced by intradermal injection of complete Freund's adjuvant (0.1 mL) into the right hind paw of Wistar albino rats. Withania somnifera root powder (1000 mg/kg/day) and Indomethacin (3 mg/kg/day) were orally administered for 8 days (from 11th to 18th day) after adjuvant injection. The anti-arthritic effect of W. somnifera root powder was assessed by measuring changes in lipid peroxidation, antioxidant status, and glycoprotein levels in plasma and spleen of arthritic animals. In addition, cartilage degradation was also assessed by estimating bone collagen, and urinary constituents in arthritic animals. Results of the present investigation showed significant increase in the level of lipid peroxides, glycoproteins, and urinary constituents with the depletion of antioxidant status and bone collagen in arthritic animals. These biochemical alterations observed were ameliorated significantly by oral administration of W. somnifera root powder (1000 mg/kg body weight) in arthritic animals. The results of this study clearly indicate that W. somnifera root powder is capable of rectifying the above biochemical changes in adjuvant arthritis.

Calcium pyrophosphate dihydrate and basic calcium phosphate crystal-induced arthropathies: update on pathogenesis, clinical features, and therapy.

Calcium-containing crystals are the most common class for the osteoarthritic joint. They are responsible for acute periarthritis and destructive arthropathies, and for tissue deposits mimicking tumor-like masses. These crystals encompassed mainly calcium pyrophosphate dihydrate and basic calcium phosphate crystals, with the latter being related to hydroxyapatite, carbonate-substituted apatite, and octacalcium phosphate. Calcification deposit mechanisms will be reviewed with respect to extracellular inorganic pyrophosphate dysregulation mainly caused by modulation of specific membrane channel disorders. Genetic defects have been extensively studied and identified mutation of specific genes such as ANKH and COL. Pathogenesis of crystal-induced inflammation is related to synovial tissue and direct cartilage activation. Besides classical knee or wrist pseudogout attacks or Milwaukee shoulder arthropathies, clinicians should be aware of other specific common presentations, such as erosive calcifications, spinal cord compression by intraspinal masses, ligamentum flavum calcification, or atypical calcified tophus. Promising clinical results for preventing calcium crystal deposits and cartilage degradation are lacking. Practical imaging tools are needed to monitor reduction of calcification of fibrocartilage and articular cartilage as markers of drug efficacy.

Chondroprotective agents: glucosamine and chondroitin.

The near universal finding of the safety of glucosamine and chondroitin combined with some compelling evidence of their efficacy should spur further research into their mechanism of action, optimal dosing, long-term effects on disease modification, and clinical applicability. When recommending a supplement to patients, the clinician should take into account the purity of the ingredients, reputation of the manufacturer, and the molecular weight of chondroitin supplied.

Interleukin-1 receptor antagonist prevents expression of the metalloproteinase-generated neoepitope VDIPEN in antigen-induced arthritis.

OBJECTIVE: To investigate the relationship between occurrence of the matrix metalloproteinase-generated neoepitope VDIPEN and proteoglycan (PG) loss in arthritis, and to examine the role of interleukin-1 (IL-1) in VDIPEN expression. METHODS: VDIPEN expression was investigated in murine antigen-induced arthritis by immunolocalization studies on joint sections. The involvement of IL-1 in VDIPEN expression was studied by blocking of IL-1 using IL-1 receptor antagonist (IL-1Ra). RESULTS: Profound PG loss was evident early in arthritis, without significant VDIPEN expression. Full expression of the neoepitope appeared after a few days, when PG depletion was severe, and disappeared at late stages when cartilage showed recovery from PG depletion. At sites where chondrocyte death occurred and cartilage did not recover from the initial cartilage depletion, VDIPEN expression remained present. Prophylactic IL-1Ra treatment of arthritic mice resulted in almost complete prevention of VDIPEN expression. However, IL-1Ra had only a minor effect on PG depletion, emphasizing that there is no correlation between VDIPEN and early PG depletion. CONCLUSION: This study indicates that IL-1 is involved in VDIPEN expression. Although VDIPEN-inducing metalloproteinases do not seem to be involved in early PG depletion during antigen-induced arthritis, metalloproteinase neoepitopes are present when PG depletion is severe.

Detection of arthritogenic factor in adjuvant arthritis.

An evocation of arthritis by an Ag-specific lymphokine has recently been considered with the description of arthritogenic factor (AF) in rats with collagen arthritis. Because rats with CFA-induced arthritis also exhibit T cell reactivity to native type II collagen, T cell lines specific for this protein were established from CFA-injected rats. Supernatant material from these lines contained a type II collagen-binding lymphokine with functional and biochemical attributes identical with those described for AF, i.e., it was a 65-kDa species cross-reacting immunoprotein possessing the ability to incite an erosive, proliferative synovitis when injected into the knee joint of naive recipients. Similarities were also observed with HPLC and on two-dimensional gels. Lymph node cells from rats with arthritis created by injection of the synthetic adjuvant, CP-20,961 failed to produce AF, suggesting that this material is not a ubiquitous concomitant of inflammatory arthritis in the rat. Test injections into sites contiguous with the ear cartilage plate and into fibroblast-lined s.c. pouches suggested that cartilage was a requisite for the induction of inflammation by AF. These data identify a potentially shared effector pathway in the collagen and adjuvant models. The presence of AF in two frequently used models further supports the hypothesis that Ag-specific lymphokines can create autoimmune disease.