The synovial membrane of the temporomandibular joint lines all the intraarticular structures except the articular cartilage of the articular eminence, fossa, the mandibular condyle and the articular disc. The synovial membrane consists of two layers. The first layer is a lining cell layer facing the joint space and called synovial intima. The second layer is called subintimal or subsynovial tissue. The synovial membrane fulfills several important functions in maintaining normal joint physiology and joint function. Synovitis occurs when the level of cellular debris and the concentration of chemical mediators of inflammation produce levels that the synovial membrane is unable to ingest, absorb or process. So degeneration of temporomandibular joint may be increased by deficiency of synovial fluid. After general anesthesia by intramuscular injection of ketamin, exposure of TMJ of rabbit was done by preauricular approach. After exposure, rubber drain was inserted into the upper joint cavity, to prevent accumulation of synovial fluid. Penicillin G was used to prevent secondary infection for 3 days. Fifteen Rabbits were used for experiment, and subdivided into 5 groups (one normal group and 4 experimental groups, each subdivided group consisted in 3 rabbits). Experimental groups were taken after period of 1, 2, 3, 4 weeks. After euthansia, enbloc excision of TMJ was done to make biopsy specimen. The results were as follows; 1. Layers of synovial intima were increased in experimental group, 8~10 layers in first week group and 4~5 layers in fourth week group as compared with 2~3 layers in normal group. 2. Inflammation, vascular change and subintimal edema were highest in second week group, but continued to fourth week group. 3. Subintimal fibrosis occured in second week group, and increased to fourth week group. 4. Due to fibrosis of joint cavity, narrowing of joint space occured in the third week group, and increased to fourth week group. 5. Degeneration of articular disc occured in second week group and increased to fourth week group.
Anesthesia, General ; Biopsy ; Cartilage, Articular ; Coinfection ; Edema ; Fibrosis ; Inflammation ; Inflammation Mediators ; Injections, Intramuscular ; Joints* ; Mandibular Condyle ; Penicillin G ; Physiology ; Rabbits* ; Rubber ; Synovial Fluid* ; Synovial Membrane ; Synovitis ; Temporomandibular Joint

There is a lack of clinical and experimental studies of the treatment of incompletely transected tendons. The controversy concerning the source of flexor tendon nutrients is of important clinical concern in healing of the injured tendon; thus, the flexor tendon blood supply has cited as a reason for using specific tendon suture techniques, and as a rationale for preserving the superficialis tendon and its vincula during tendon repair surgery. Our knowledge of the normal physiology of digital flexor tendons and the mechanism of their healing process is deficient. The aim of this study was to investigate the relative importance of the synovial fluid and the blood supply respectively for the healing of partially severed flexor tendons. We observed the sequential histological and vascular changes which occur in healing of the partial lacerations in the dorsal and plantar aspects of the tendons. We observed the vascularities of the two partially severed tendon groups after injection of microfil and india ink through the femoral artery. In the healing process there was no sequential histological difference between the dorsal and the plantar severed tendons. The vascularity patterns of the healing tendons were significantly increased and the hypervascularity of dorsal severed tendons was greater than that of plantar severed tendons. Partially severed tendons were completely healed without surgical repair with dense collagen fibers without adhesion in most cases. We concluded from this study that the blood vessels appeared to play a significant role in the healing of the severed flexor tendons. An intact synovial environment did not seem to be required for healing of the severed tendon. It is not necessary to surgically repair the partially severed tendon for prevention of rupture and adhesion.
Adhesions/etiology ; Animal ; Chickens ; Comparative Study ; Support, Non-U.S. Gov't ; Synovial Fluid/physiology ; Tendon Injuries/*physiopathology ; Tendons/blood supply ; *Wound Healing

BACKGROUNDProgrammed cell death 5 (PDCD5) is a novel apoptotic regulatory gene that promotes apoptosis in various tumor cells. Studies have shown that PDCD5 accelerates the apoptosis of synoviocytes in vitro, implying a potential role in rheumatoid arthritis (RA) pathogenesis. This study examined the expression of PDCD5 in serum and synovial fluid of RA patients, its effect on the expression of inflammatory cytokine, interleukin-17 (IL-17), and the assessment of disease activity in RA.

METHODSPDCD5 and IL-17 levels in serum and synovial fluid from 18 patients with RA and 22 patients with osteoarthritis (OA) were detected using enzyme-linked immunosorbent assay (ELISA). Concentrations of serum PDCD5 in 40 healthy people were also detected as controls. As disease activity indices, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), rheumatoid factor (RF), and X-ray grading scale were also evaluated.

RESULTSSerum and synovial fluid PDCD5 levels in RA patients were significantly higher than those in OA and healthy controls. Serum PDCD5 level was inversely correlated to CRP and ESR, and was significantly higher in the RF negative group than in the positive group. PDCD5 level was also negatively correlated with IL-17 levels both in serum and synovial fluid of RA patients. However, differences in synovial fluid PDCD5 level from RA patients at different Larsen stages were not detectable.

CONCLUSIONSPDCD5 affects RA pathogenesis. Insufficient apoptosis of fibroblast-like synoviocytes and inflammatory cells in RA could increase the expression of PDCD5 protein. As PDCD5 levels correlated negatively with disease activity indices and IL-17 level, PDCD5 could become a target in the diagnosis and treatment of RA.

Aged ; Apoptosis ; Apoptosis Regulatory Proteins ; analysis ; blood ; physiology ; Arthritis, Rheumatoid ; etiology ; Blood Sedimentation ; C-Reactive Protein ; analysis ; Female ; Humans ; Interleukin-17 ; analysis ; blood ; physiology ; Male ; Middle Aged ; Neoplasm Proteins ; analysis ; blood ; physiology ; Synovial Fluid ; chemistry

BACKGROUNDOsteoarthritis (OA) is a chronic and incurable disease, lacking effective treatment. Gene therapy offers a radical different approach to the treatment of arthritis. Even though the etiology of OA remains unclear, there is now considerable evidence to suggest that interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha) are the main mediators in the pathogenesis of OA. The goal of this study was to determine the efficacy of local expression of interleukin-1 receptor antagonist (IL-1Ra) and soluble tumor necrosis factor-alpha receptor type I (sTNF-RI) by direct adenoviral-mediated intra-articular gene delivery in the rabbit model of osteoarthritis.

METHODSAdenoviral vectors containing IL-1Ra or sTNF-RI genes were constructed. OA was induced in both hind knees of 12 New Zealand white rabbits by the excision of the medial collateral ligament plus medial meniscectomy. Five days after surgery, approximately 1 x 10(8) plaque-forming units (pfu) of adenovirus were injected into the joint space of the knee through the patellar tendon. A total of 12 operated rabbits were divided into four groups. Three experimental rabbit groups received 1 x 10(8) pfu of adenovirus encoding either IL-1Ra (3 rabbits), sTNF-RI (3 rabbits) or IL-1Ra and sTNF-RI in combination (3 rabbits), into both knee joints respectively. An inflamed control group of 3 rabbits received approximately 1 x 10(8) pfu of Ad-GFP into both joints. Three days after injection of the adenovirus, both knees of each rabbit were lavaged with 1 ml of saline solution through the patellar tendon. At day 7, the rabbits were sacrificed, and the knees were lavaged, dissected and analyzed for effects of transgene expression. Levels of IL-1Ra and sTNF-RI expression in recovered lavage fluids were measured using a cytokine ELISA kit. Cartilage from the lesion areas of medial femoral condyle and synovium were fixed, embedded, sectioned and stained with hematoxylin and eosin (cartilage and synovium) and toluidine blue (cartilage). The samples were examined by light microscopy and quantitatively evaluated.

RESULTSIntra-articular delivery of IL-1Ra resulted in a significant inhibition of cartilage degradation, but did not affect synovial changes. In contrast, rabbit knee joints receiving sTNF-RI alone showed no detectable reduction in cartilage degradation. However, double gene transfer of IL-1Ra and sTNF-RI resulted in a higher suppression of the cartilage degradation and an observable reduction in synovitis. These data add to and confirm that IL-1Ra has good chondroprotective properties, but TNF-alpha blockade has little effect on joint destruction.

CONCLUSIONThe enhanced therapeutic effects of both antagonists in combination suggest inhibition of multiple inflammatory cytokines may be more efficacious than blockade of either cytokine alone in treating OA.

Adenoviridae ; genetics ; Animals ; Arthritis, Experimental ; genetics ; therapy ; Cartilage ; metabolism ; pathology ; Cartilage, Articular ; metabolism ; pathology ; Cell Line ; Cells, Cultured ; Genetic Therapy ; methods ; Genetic Vectors ; genetics ; Humans ; Interleukin 1 Receptor Antagonist Protein ; Osteoarthritis ; genetics ; therapy ; Rabbits ; Receptors, Tumor Necrosis Factor, Type I ; genetics ; physiology ; Sialoglycoproteins ; genetics ; physiology ; Synovial Fluid ; metabolism ; Synovial Membrane ; cytology ; metabolism ; Transfection ; methods

OBJECTIVETo examine the expression of proteoglycan 4 (PRG-4) induced by hydrostatic pressure in rat temporomandibular synovial fibroblasts and investigate the possible mechanism.

METHODSThe cultured rat temporomandibular synovial fibroblasts were subjected to 100 kPa magnitude intermittent hydrostatic pressure (IHP) at frequency of 4 h/day, and the static group served as control. The expressions of Smad pathway proteins and p38MAPK pathway proteins were analyzed by Western blot and immunofluorescence staining. Then the cells were incubated with SB431542, the inhibitor of transforming growth factor (TGF)-β receptor. Western blot and reverse transcription PCR were used to detect the PRG-4 expression after 72 h.

RESULTSThe expression of phosphorylated Smad-2 and phosphorylated Smad-3 were increased after 1 h of IHP, reaching a maximum after 2 h and 4 h of IHP, respectively.However, the protein content of phosphorylated p38 did not vary significantly. In addition, IHP induced nuclear translocation of Smad-2/-3, and the immunofluorescence staining signal intensity markedly increased (24.11 ± 4.70)(P < 0.05). The levels of PRG-4 mRNA were significantly increased by IHP (1.48 ± 0.08)(P < 0.05). Treatment of cells with SB431542 could decrease the expression of PRG-4 mRNA significantly after IHP (0.47 ± 0.05)(P < 0.05). In addition, SB431542 inhibited the expression of PRG-4 protein induced by IHP.

CONCLUSIONSSmad signal acts as an essential signal pathway to regulate PRG-4 expression induced by IHP.

Animals ; Cells, Cultured ; Fibroblasts ; Hydrostatic Pressure ; Phosphorylation ; Protein-Serine-Threonine Kinases ; Proteoglycans ; biosynthesis ; RNA, Messenger ; Rats ; Receptors, Transforming Growth Factor beta ; Signal Transduction ; Smad Proteins ; physiology ; Synovial Fluid ; metabolism ; Temporomandibular Joint ; metabolism ; p38 Mitogen-Activated Protein Kinases