transforming-growth-factor-beta and Temporomandibular-Joint-Disorders

The objective of this review was to assess the literature for evidence investigating the role of TGF-β in temporomandibular joint disease with osteoarthritis.. An electronic and manual search was carried out on the databases, MEDLINE/PubMed, Cochrane Library, Web Of Science, and EMBASE, from 1975 to December 2015 by two independent evaluators to identify clinical and laboratory trials in English.. The search produced 693 records. Following a process of selection based on certain criteria, eight articles were included.. This systematic review suggests that TGF-β administration alone does not result in joint regeneration; other factors may be involved, such as TGF-β receptor expression ,and TGF-β receptor mutations that do not allow a correct transduction, resulting in TGF-β deficiency. The anabolism induced by this growth factor is also able to neutralize the catabolic processes that are elevated in osteoarthritis. Therefore, further studies are essential to determine how the concentration of TGF-β in the temporomandibular joints acts as a potential marker for the development of degenerative conditions.

Topics: Animals; Biomarkers; Databases, Factual; Humans; Metabolism; Mutation; Osteoarthritis; Receptors, Transforming Growth Factor beta; Temporomandibular Joint; Temporomandibular Joint Disorders; Transforming Growth Factor beta

Patients with temporomandibular dysfunction (TMD) usually suffer from pathology or malpositioning of the temporomandibular joint (TMJ) disk, leading to the degenerative lesion of condyles. Kartogenin can promote the repair of damaged cartilage. This study aimed to explore whether intra-articular injection of kartogenin could alleviate the TMJ injury induced by type II collagenase. We measured the head withdrawal threshold and found that kartogenin alleviated the pain around TMD induced by type II collagenase. We observed the morphology of the condylar surface and found that kartogenin protected the integration of the condylar surface. We analyzed the density of the subchondral bone and found that kartogenin minimized the damage of TMJ injury to the subchondral bone. We next explored the histological changes and found that kartogenin increased the thickness of the proliferative layer and more collagen formation in the superficial layer. Then, to further ensure whether kartogenin promotes cell proliferation in the condyle, we performed immunohistochemistry of proliferating cell nuclear antigen (PCNA). The ratio of PCNA-positive cells was significantly increased in the kartogenin group. Next, immunofluorescence of TGF-β1 and SMAD3 was performed to reveal that kartogenin activated the TGF-β/SMAD pathway in the proliferative layer. In conclusion, kartogenin may have a therapeutic effect on TMJ injury by promoting cell proliferation in cartilage and subchondral bone. Kartogenin may be promising as an intra-articular injection agent to treat TMD.

Topics: Animals; Cartilage, Articular; Chondrocytes; Collagenases; Humans; Mandibular Condyle; Osteoarthritis; Proliferating Cell Nuclear Antigen; Rats; Temporomandibular Joint; Temporomandibular Joint Disorders; Transforming Growth Factor beta

Emerging evidence has implied that subchondral bone plays an important role during osteoarthritis (OA) pathology. This study was undertaken to investigate whether abnormalities of the condylar subchondral bone lead to temporomandibular joint (TMJ) OA. We used an osteoblast-specific mutant TGF-β1 transgenic mouse, the CED mouse, in which high levels of active TGF-β1 occur in bone marrow, leading to abnormal bone remodeling. Subchondral bone changes in the mandibular condyles were investigated by micro-CT, and alterations in TMJ condyles were confirmed by histopathological and immunohistochemical analysis. Abnormalities in the condylar subchondral bone, characterized as fluctuant bone mineral density and microstructure and increased but uncoupled activity of osteoclasts and osteoblasts, were apparent in the 1- and 4-month CED mouse groups, while obvious cartilage degradation, in the form of cell-free regions and proteoglycan loss, was observed in the 4-month CED group. In addition, increased numbers of apoptotic chondrocytes and MMP9- and VEGF-positive chondrocytes were observed in the condylar cartilage in the 4-month CED group, but not in the 1-month CED group, compared with their respective age-matched controls. This study demonstrated that progressive degradation of mandibular condylar cartilage could be induced by the abnormal remodeling of the underlying subchondral bone during TMJOA progression.

Topics: Animals; Apoptosis; Bone Density; Bone Marrow; Bone Remodeling; Cartilage; Case-Control Studies; Caspase 3; Chondrocytes; Collagen Type I; Disease Models, Animal; Gene Expression Regulation; Mandibular Condyle; Matrix Metalloproteinase 13; Matrix Metalloproteinase 9; Mice; Mice, Inbred C57BL; Mice, Inbred Strains; Mice, Transgenic; Osteoarthritis; Osteoblasts; Osteoclasts; Proteoglycans; Temporomandibular Joint Disorders; Transforming Growth Factor beta; Vascular Endothelial Growth Factor A; X-Ray Microtomography

The goal of this study was to investigate changes in nerve growth factor (NGF) and its high-affinity receptor-tropomyosin receptor kinase A (TrkA) expression in the TMJ after intra-articular inflammation.. We employed the Col1-IL1β(XAT) inducible model of joint inflammation. Changes in NGF and TrkA expression were evaluated by immunohistochemistry. The function of NGF on cell differentiation was assessed in vitro employing the ATDC5 chondrocyte cell line.. NGF expression was observed in articular chondrocytes only after TMJ inflammation, whereas TrkA expression was detected in articular chondrocytes under both naïve as well as inflamed conditions. The potential effect of NGF on articular chondrocytes was studied on the ATDC5 cell line, whereby NGF decelerated the maturation rate of this chondrogenic cell line, presumably by arresting cell differentiation at the prehypertrophic stage of chondrocyte maturation.. NGF-TrkA signaling in the TMJ provides potentially a means of protection against the development of osteoarthritis by decelerating chondrocyte differentiation. This discovery may lead to the development of novel therapies for osteoarthritis of the TMJ and other joints.

Topics: Alkaline Phosphatase; Animals; Arthritis; Cartilage, Articular; Cell Culture Techniques; Cell Differentiation; Cell Line; Cell Proliferation; Chondrocytes; Collagen Type I; Collagen Type II; Disease Models, Animal; Hypertrophy; Interleukin-1beta; Mice; Mice, Inbred C57BL; Mice, Transgenic; Nerve Growth Factor; Receptor, trkA; Signal Transduction; Temporomandibular Joint Disorders; Transforming Growth Factor beta; Transgenes

AIM OF STUDY was complex detection of appearance and distribution of growth factors, facial bone growth stimulating genes, ground substance proteins and apoptosis in bone of ankylotic TMJ in primary and repeatedly operated children.. Ankylotic tissue was obtained during the arthroplastic surgery from two 6 years old children (boy and girl) with osseous type of disease. The girl underwent the repeated surgery in TMJ due to the same diagnosis in age of 12 years. Ankylotic tissue was proceeded for detection of BMP2/4, TGFβ, Msx2, osteopontin, osteocalcin immunohistochemically, and apoptosis. RESULTS demonstrated massive bone formation intermixed by neochondrogenesis the lack of BMP 2/4, but abundant number of TGFβ-containing cells in bone of all tested cases. Despite rich osteopontin positive structures in bone obtained from both - primary and repeated surgery, osteocalcin demonstrated variable appearance in 6 years aged children, but was abundant in joint 5 years later during disease recurrence. Expression of Msx2 varied widely before, but with tendency to decrease stabilized until few positive cells in bone of 12 years old girl. Apoptosis practically was not detected in primarily operated TMJ, but massively affected the supportive tissue in girl with recurrent ankylosis.. The lack of BMP2/4 expression in ankylotic bone proves the disorders in cellular differentiation with simultaneous compensatory intensification of cellular proliferation and/or growth by rich expression of TGFβ leading to the remodelling of TMJ. Mainly rich distribution of osteocalcin and osteopontin indicate the intensive mineralization processes of ankylotic bone. Persistent Msx2 expression is characteristic for the supportive tissue of recurrent ankylosis of TMJ and indicates the persistent stimulation of bone growth compensatory limitated by massive increase of programmed cell death.

Topics: Ankylosis; Apoptosis; Arthroplasty; Bone Development; Bone Morphogenetic Protein 2; Bone Morphogenetic Protein 4; Bone Remodeling; Calcification, Physiologic; Cell Differentiation; Cell Proliferation; Child; Chondrogenesis; Female; Homeodomain Proteins; Humans; Intercellular Signaling Peptides and Proteins; Male; Osteocalcin; Osteocytes; Osteogenesis; Osteopontin; Recurrence; Reoperation; Temporomandibular Joint; Temporomandibular Joint Disorders; Transforming Growth Factor beta

Similarly to humans, healthy, wild-type mice develop osteoarthritis, including of the temporomandibular joint (TMJ), as a result of aging. Pro-inflammatory cytokines, such as IL-1beta, IL-6, and TNFalpha, are known to contribute to the development of osteoarthritis, whereas TGFbeta has been associated with articular regeneration. We hypothesized that a balance between IL-1beta and TGFbeta underlies the development of TMJ osteoarthritis, whereby IL-1beta signaling down-regulates TGFbeta expression as part of disease pathology. Our studies in wild-type mice, as well as the Col1-IL1beta(XAT) mouse model of osteoarthritis, demonstrated an inverse correlation between IL-1beta and TGFbeta expression in the TMJ. IL-1beta etiologically correlated with joint pathology, whereas TGFbeta expression associated with IL-1beta down-regulation and improvement of articular pathology. Better understanding of the underlying inflammatory processes during disease will potentially enable us to harness inflammation for orofacial tissue regeneration.

Topics: Animals; Down-Regulation; Female; Interleukin-1beta; Male; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Mice, Transgenic; Osteoarthritis; Signal Transduction; Temporomandibular Joint; Temporomandibular Joint Disorders; Transforming Growth Factor beta

This study aimed to examine the effect of injection of transforming growth factor beta (TGF-beta) on articular cartilage in osteoarthritic temporomandibular joint (TMJ).. Disc perforation was performed bilaterally in 24 rabbits to induce osteoarthritis (OA). The right joint was injected with TGF-beta as experimental groups, and the left joint with physiologic saline as control. Animals were killed at different intervals. Histology and reverse transcriptase polymerase chain reaction was performed for comparison.. All joints showed OA-like changes, but the degree in the experimental was significantly less severe than in the control. At 12 weeks a significantly greater expression of aggrecan and collagen type II was found in the experimental compared with the control joints. However, no difference in either anabolic or catabolic genes was found between the two groups at 24 weeks.. Transforming growth factor beta may have a potential benefit in protecting articular cartilage during the development of TMJ OA.

Topics: Aggrecans; Animals; Arthritis, Experimental; Cartilage, Articular; Collagen Type II; Endopeptidases; Fibrocartilage; Glyceraldehyde-3-Phosphate Dehydrogenases; Interleukin-1; Mandibular Condyle; Osteoarthritis; Rabbits; Temporomandibular Joint; Temporomandibular Joint Disorders; Time Factors; Transforming Growth Factor beta

A histopathological study of 30 cases of synovial osteochondromatosis found that the process followed a temporal sequence characterised by three phases: (I) active intrasynovial disease only; (II) transitional lesions with both active intrasynovial proliferation and free loose bodies; and (III) many free osteochondral bodies with no demonstrable intrasynovial disease [J. Bone Joint Surg. 59 (1977) 792]. We present five cases of synovial chondromatosis of the temporpmandibular joint (TMJ) which we studied by immunohistochemical methods of for transforming growth factor beta (TGFbeta) and tenascin.

Topics: Adult; Chondromatosis, Synovial; Female; Humans; Immunohistochemistry; Joint Loose Bodies; Temporomandibular Joint Disorders; Tenascin; Transforming Growth Factor beta

The purpose of this study was to investigate the therapeutic use of recombinant human bone morphogenetic protein-2 (rhBMP-2) in internally deranged temporomandibular joints (TMJ). Defects (2 mm in diameter) were created in the surface of the condylar head. Lyophilized rhBMP-2 with collagen as the carrier was implanted in the defects in different doses: rhBMP-2 15 microg (n = 5); rhBMP-2 3 microg (n = 5); rhBMP-2 0.6 microg (n = 5). In the two control groups, the defects were either filled with collagen alone (n = 5) or left untreated (n = 5). Three weeks postoperatively the sites of defects were examined under light microscopy. In the 15 micromg and the 3 microg groups, new cartilage had filled the defects; endochondral ossification was also found deep within the defect. In the 0.6 microg group, fibrous tissue was proliferating in most areas of the defect, although cartilage was also found in some parts. In the two control groups, there was either soft tissue repair only or no evidence of tissue repair. These findings suggest that BMP-2 could stimulate the repair of defects in the articular cartilage of the mandibular condyle head during the 3 weeks postoperatively. To observe the progress of endochondral ossification in more detail, it may be necessary to extend the experiment for a longer period of time. However, this study supports the contention that BMP-2 may be useful in the regeneration of cartilage in TMJ disease.

Topics: Animals; Bone Morphogenetic Protein 2; Bone Morphogenetic Proteins; Cartilage Diseases; Cartilage, Articular; Chondrocytes; Chondrogenesis; Collagen; Connective Tissue; Drug Carriers; Drug Implants; Humans; Mandibular Condyle; Osteogenesis; Rabbits; Recombinant Proteins; Regeneration; Temporomandibular Joint Disc; Temporomandibular Joint Disorders; Time Factors; Transforming Growth Factor beta; Wound Healing

This study was undertaken to examine the presence of interleukin-1 receptor antagonist (IL-1ra), IL-10, and transforming growth factor-beta1 (TGF-beta1) in the synovial fluid (SF) lavage specimens of patients with temporomandibular disorders (TMDs).. Synovial fluid lavage specimens were obtained from 14 temporomandibular joints (TMJs) of 12 patients with TMJ internal derangement (ID) and 17 TMJs of 15 patients with TMJ osteoarthritis (OA). Seven synovial fluid lavage samples of TMJs of four asymptomatic donors served as normal controls. The concentrations of IL-1ra, IL-10, and TGF-beta1 were detected with sensitive and specific sandwich enzyme-linked immunosorbent assay (sandwich-ELISA).. IL-1ra, IL-10, and TGF-beta1 in all the normal controls were undetectable. IL-1ra concentrations were 175.78 +/- 52.43 pg/mL in the patients with TMJ ID and 187.85 +/- 59.51 pg/mL in those with TMJ OA. IL-10 was undetectable in all the TMJ ID and OA samples. The concentration of TGF-beta1 in TMJ ID patients (47.93 +/- 88.25 pg/mL) was significantly less than in patients with TMJ OA (143.61 +/- 108.00 pg/mL) (P < .01).. The results suggest that deficiencies of IL-1ra, IL-10, and TGF-beta1 probably play an important role in the cause and pathogenesis of TMJ ID and OA.

Topics: Adolescent; Adult; Chronic Disease; Enzyme-Linked Immunosorbent Assay; Female; Humans; Interleukin 1 Receptor Antagonist Protein; Interleukin-10; Male; Middle Aged; Osteoarthritis; Receptors, Interleukin-1; Sensitivity and Specificity; Sialoglycoproteins; Synovial Fluid; Temporomandibular Joint; Temporomandibular Joint Disorders; Therapeutic Irrigation; Transforming Growth Factor beta

We examined the expression of the transforming growth factor beta (TGF-beta) in 28 human temporomandibular joint (TMJ) samples (internal derangement of TMJ and control specimens) by an immunohistological method using paraffin-embedded tissues and a polyclonal antibody specific to human TGF-beta. The resulting reaction of TGF-beta expression divided into three types as follows. The first type, around the fibrocyte and in the lacunae of chondrocytes in the disc. The second type, at the stroma of the mildly hypertrophic synovial membrane and severely hypertrophic synovial membrane. The first type was observed in all the cases including the control cases. The second type showed only in the internal derangement of TMJ, and its expression pattern resembled that of tenascin (TN) within the stroma of hypertrophic synovial membranes. In conclusion, TGF-beta and TN were distributed in the affected synovial membrane of TMJ with internal derangement. These findings suggested that TGF-beta and TN might have a close relationship with synovitis, followed by tissue repair.

Topics: Adult; Aged; Female; Humans; Hypertrophy; Immunohistochemistry; Male; Middle Aged; Synovial Membrane; Temporomandibular Joint; Temporomandibular Joint Disorders; Tenascin; Transforming Growth Factor beta

The purpose of this study was to analyze the expression of bone morphogenetic protein-2 (BMP-2) in patients with internal derangement of the temporomandibular joint.. Twenty-one human temporomandibular joint samples (5 extirpated disks and 16 biopsy specimens of synovitis area from patients with internal derangement of the TMJ) and 2 control temporomandibular joint specimens (2 normal disks obtained by autopsy) were analyzed with specific antibodies through use of an immunohistochemical technique.. BMP-2 was predominantly localized in chondrocytes around the damaged areas of the articular disks. BMP-2 expression was also found in synovial cells and endothelial cells of blood vessels. Control specimens demonstrated BMP-2 staining in synovial lining cells and endothelial cells of blood vessels. However, the chondrocytes in the normal cartilage layers of the control specimens showed no staining.. These findings suggest that BMP-2 may be involved in the pathogenesis of osteoarthritic changes or the repair process of temporomandibular joint internal derangement.

Topics: Adult; Biopsy; Bone Morphogenetic Protein 2; Bone Morphogenetic Proteins; Humans; Immunohistochemistry; Osteoarthritis; Synovial Membrane; Temporomandibular Joint; Temporomandibular Joint Disc; Temporomandibular Joint Disorders; Transforming Growth Factor beta

Osteoarthritic lesions were observed in the mandibular condyle cartilage of mice aged 7 months and older. These lesions appeared as fibrillations along the articular surface and were accompanied by reduced extracellular matrix synthesis and chondrocyte proliferation. Explants of mandibular condyle cartilage were cultured in serum-free BGJb medium supplemented with ascorbic acid (300 micrograms/ml), penicillin (100 U/ml) and streptomycin (100 micrograms/ml) for up to 72 h. Cultures were further supplemented with either hTGF-beta 1 (0.1-5.0 ng/ml) or human IL-1 alpha (40 U/ml). [3H]thymidine (2 microCi/ml) and [35S]SO4 (10 microCi/ml) were added to the culture medium for the last 24 h of culture and incorporation into DNA and sulfated proteoglycans, respectively, studied. The results indicated that protein and DNA contents, [3H]thymidine and [35S]SO4 incorporation, as well as the specific activity of alkaline phosphatase, were increased by TGF-beta 1. Addition of 1.0 or 5.0 ng/ml hTGF-beta 1 to the cultures for 48 h, had the most stimulatory effect on matrix synthesis and cell proliferation, whereas 0.1 ng/ml hTGF-beta 1 appeared to be inhibitory when compared to controls. Increased [35S]SO4 labeling of chondrocyte clusters was observed by autoradiography in tissue sections from cultures treated with TGF-beta 1 (1.0 and 5.0 ng/ml). In contrast, IL-1 alpha exerted inhibitory effects on cell proliferation and matrix synthesis. However, it induced the activity of acid phosphatase in these cultures. The results of the present study show that IL-1 alpha had catabolic effect on his tissue, while TGF-beta 1 enhanced proliferation and induced synthetic activity of the cartilage cells. Such action by TGF-beta suggests the existance of a possible repair process in osteoarthritic cartilage of the temporo-mandibular joint of aged mice.

Topics: Aging; Animals; Cartilage, Articular; DNA; Extracellular Matrix; Female; Humans; Interleukin-1; Mandibular Condyle; Mice; Mice, Inbred ICR; Osteoarthritis; Proteins; Temporomandibular Joint; Temporomandibular Joint Disorders; Transforming Growth Factor beta

Synovial chondromatosis (SC) is an uncommon, benign condition of unknown etiology. A case of SC of the temporomandibular joint (TMJ) with the immunohistochemical findings of transforming growth factor-beta (TGF) and tenascin (TN) is reported. The roles of TGF and TN in SC of TMJ are discussed.

Topics: Adult; Arthroscopy; Cartilage, Articular; Chondromatosis, Synovial; Collagen; Coloring Agents; Endoscopy; Extracellular Matrix; Female; Humans; Hyperplasia; Immunoenzyme Techniques; Joint Loose Bodies; Synovial Membrane; Temporomandibular Joint Disorders; Tenascin; Transforming Growth Factor beta