transforming-growth-factor-beta and Ankylosis

The tooth is stabilized by fiber-rich tissue called the periodontal ligament (PDL). The narrow space of the PDL does not calcify in the physiological state even thought it exists between two calcified tissues, namely, the cementum of the root and alveolar bone. Two situations that require PDL regeneration are periodontitis and dental trauma. Periodontitis induces the loss of PDL and alveolar bone due to inflammation related to infection. Conversely, in PDLs damaged by dental trauma, accelerating bone formation as an overreaction of the healing process is induced, thereby inducing dentoalveolar ankylosis at the tooth root surface. PDL regeneration following dental trauma must therefore be considered separately from periodontitis. Therefore, PDL regeneration in dental trauma must be considered separately from periodontitis. This review focuses on the components involved in avoiding dentoalveolar ankylosis, including oxytalan fibers, aggregated microfibrils, epithelial cell rests of Malassez (ERM), and TGF-β signaling. During root development, oxytalan fibers produced by PDL cells work in collaboration with the epithelial components in the PDL (e.g., Hertwig's root sheath [HERS] and ERM). We herein describe the functions of oxytalan fibers, ERM, and TGF-β signals which are involved in the avoidance of bone formation.

Topics: Ankylosis; Fibrillins; Humans; Periodontal Ligament; Periodontitis; Tooth Ankylosis; Transforming Growth Factor beta

To investigate p38 mitogen activated protein kinase (MAPK) signalling in an in vitro model of bone morphogenetic protein (BMP) and transforming growth factor β (TGFβ)-induced chondrogenesis and in vivo, with specific attention to its potential role in ankylosing enthesitis.. Human periosteum-derived cells (hPDCs) were cultured in pellets and stimulated with BMP2 or TGFβ1 in the presence or absence of a p38 inhibitor SB203580 or proinflammatory cytokines. Chondrogenic differentiation was evaluated using quantitative PCR. Male DBA/1 mice from different litters were caged together at the age of 8 weeks and treated with SB203580 in both a preventive and therapeutic strategy. The mice were evaluated for prospective signs of arthritis and the toe joints were analysed histologically to assess disease severity.. p38 inhibition by SB203580 and proinflammatory cytokines downregulated chondrogenic markers in pellet cultures stimulated by BMP2 or TGFβ1. In contrast, the in vivo experiments resulted in an increased clinical incidence of arthritis and pathology severity score, reflecting progression towards ankylosis in mice given SB203580.. Inhibition of p38 inhibited chondrogenic differentiation of progenitor cells, showing that not only the SMAD signalling pathways and also alternative activation of MAPKs including p38 contribute to chondrogenesis. Such an inhibitory effect is not found in an in vivo model of joint ankylosis and spondyloarthritis. Increased incidence and severity of disease in preventive experiments and shifts in disease stages in a therapeutic experimental set-up suggest that specific inhibition of p38 may have deleterious rather than beneficial effects.

Topics: Animals; Ankylosis; Bone Morphogenetic Proteins; Cell Proliferation; Cells, Cultured; Chondrocytes; Chondrogenesis; Disease Models, Animal; Enzyme Activation; Enzyme Inhibitors; Gene Expression; Imidazoles; Male; Mice; Mice, Inbred DBA; p38 Mitogen-Activated Protein Kinases; Periosteum; Pyridines; Signal Transduction; Smad Proteins; Spondylitis, Ankylosing; Transforming Growth Factor beta

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

Osteogenic protein-1 (OP-1) is a member of the transforming growth factor beta superfamily and is a potent modulator of osteogenesis and bone cell differentiation. This preclinical study in dogs sought to assess the effects of OP-1 on periodontal wound healing in surgically created critical size Class III furcation defects. Eighteen male beagle dogs were subjected to the creation of bilateral mandibular 5 mm osseous defects. A split-mouth design was utilized which randomly assigned opposing quadrants to control therapy (surgery alone or collagen vehicle) or 1 of 3 ascending concentrations of OP-1 in a collagen vehicle (0.75 mg OP-1/g collagen, 2.5 mg/g, or 7.5 mg/g). Thus, 9 quadrants per test group received OP-1, 9 quadrants per control group received surgery alone, and 9 quadrants received collagen vehicle alone. Test articles were delivered by a surgeon masked to the treatment, and fluorogenic bone labels were injected at specified intervals post-treatment. Eight weeks after defect creation and OP-1 delivery, tissue blocks of the mandibulae were taken for masked histomorphometric analysis to assess parameters of periodontal regeneration (e.g., bone height, bone area, new attachment formation, and percent of defect filled with new bone). Histomorphometry revealed limited evidence of osteogenesis, cementogenesis, and new attachment formation in either vehicle or surgery-alone sites. In contrast, sites treated with all 3 concentrations of OP-1 showed pronounced stimulation of osteogenesis, regenerative cementum, and new attachment formation. Lesions treated with 7.5 mg/g of OP-1 in collagen regenerated 3.9+/-1.7 mm and 6.1+/-3.4 mm2 (mean +/-S.D.) of linear bone height and bone area, respectively. Furthermore, these differences were statistically different from both control therapies for all wound healing parameters (P < 0.0001). No significant increase in tooth root ankylosis was found among the treatment groups when compared to the surgery-alone group. We conclude that OP-1 offers promise as an attractive candidate for treating severe periodontal lesions.

Topics: Alveolar Process; Animals; Ankylosis; Bone Density; Bone Morphogenetic Protein 7; Bone Morphogenetic Proteins; Collagen; Dental Cementum; Disease Models, Animal; Dogs; Fluoresceins; Fluorescent Dyes; Furcation Defects; Humans; Male; Mandible; Osteogenesis; Periodontal Attachment Loss; Pharmaceutical Vehicles; Random Allocation; Recombinant Proteins; Regeneration; Single-Blind Method; Tooth Diseases; Tooth Root; Transforming Growth Factor beta; Wound Healing

Murine progressive ankylosis (MPA) is a spontaneous arthropathy that produces ankylosis of peripheral and spinal joints in mice homozygous for the gene ank. This animal model bears a striking resemblance clinically, radiographically, and histologically to ankylosing spondylitis. Phosphocitrate (PC) is the only treatment known to significantly delay disease progression in MPA. Transforming growth factor-beta (TGF-beta) is important for both developmental bone formation and fracture healing, and has been detected in biopsy specimens from sacroiliac joints of patient with ankylosing spondylitis. We hypothesized that TGF-beta might be involved in the pathogenesis of MPA.. We compared the proliferative response of resting fibroblasts from normal and MPA mice to TGF-beta 1 as measured by 3H-thymidine incorporation and the effect of PC on that response. Cells were cultured with 10% serum as a positive control. The mouse fibroblast cell line, BALB/3T3, controlled for culture conditions.. MPA and normal fibroblasts responded similarly to serum. MPA fibroblasts proliferated significantly better in TGF-beta 1 than the poorly responsive normal mouse fibroblasts. PC, at 10(-3) mol/L, inhibited the TGF-beta 1-induced proliferation of MPA and 3T3 cells, but had no effect on normal fibroblasts.. MPA fibroblasts proliferate excessively to TGF beta 1 in vitro. This effect could be caused by altered TGF receptors, changes in signal transduction, or impaired inhibition of the TGF-beta signal. This excessive response is blocked by PC. These results give further clues as to how PC inhibits the progression of ankylosis in MPA.

Topics: 3T3 Cells; Animals; Ankylosis; Cell Division; Citrates; Dose-Response Relationship, Drug; Fibroblasts; Mice; Transforming Growth Factor beta