Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0003090 (arthrodesis)
 8,374 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The potential of periodontal ligament-derived tissues to regenerate periodontal attachment after cryosurgical trauma to the PDL in dogs was evaluated. The buccal alveolar plate of each canine tooth was exposed by a semi-lunar excision. A 3 mm thick cryoprobe, cooled to -81 degrees C, was placed on the bone 5 mm apical to the crest for 10 s. This induced cellular devitalization in the bone directly in contact with the probe and the PDL under it. The freezing-thawing cycle was repeated 3 times. Control sites were sham-operated at room temperature. Histologic sections from the center of the lesions were obtained from 1 h, 48 h and 30 d specimens. 1-h control and experimental histologic sections were similar. At 48 h post-surgery, the cellular component of the frozen PDL could not be identified and inflammatory response was minimal. The collagenous framework, however, appeared to form a continuum between the alveolar bone and cementum. Lacunae in the bone at the frozen segment were empty. The injured PDL was surrounded by normal PDL. Control specimens appeared normal. At 30 d, the PDL space in the frozen segments was populated by PDL-like tissue which did not differ significantly from the PDL coronal or apical to it. Collagen fibers appeared to be attached to the cementum on one side and to the alveolar bone on the other. Bone resorption or ankylosis was not observed in the experimental sites. It is suggested that the extracellular matrix in the devitalized area was preserved, supporting regeneration of the cryolesion.
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PMID:Healing of sites within the dog periodontal ligament after application of cold to the periodontal attachment apparatus. 189 49

Previously, we demonstrated that the inductive properties of bone morphogenetic protein (BMP) highly depend on the nature of the carrier material used for implantation. In this paper, we show that administration of BMP incorporated in a fibrous collagen membrane can help to regenerate periodontal ligament and cementum both in cat canines and in monkey molars. The partially purified bovine BMP was combined with one or two layers of a fibrous collagen membrane. Although the single layer approach showed partial regeneration of periodontal defects, it also quite often led to ankylosis. The double layer technique in artificially prepared class III furcation defects in monkey molars gave favorable results. After 12 wk, not only the alveolar process but also the periodontal ligament and cementum had regenerated along the entire treated dentin surface. Collagen fibers were arranged more or less perpendicular to the surface of the new cementum. Ankylosis was not seen. It is concluded that the double-layer approach is superior to the single-layer technique in regenerating cementum.
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PMID:Regeneration of periodontal ligament and cementum by BMP-applied tissue engineering. 954 Dec 26

This study utilized three-dimensional micro-computed tomography (micro-CT) to evaluate the regenerative response to Bio-Oss Collagen when used alone or in combination with a Bio-Gide bilayer collagen membrane for the treatment of four intrabony defects (5 to 7 mm) around single-rooted teeth. The micro-CT observations are compared to the clinical, radiographic, and histologic results, which have been previously reported. After reflecting a full-thickness flap, thorough degranulation and root planing were accomplished. Bio-Oss Collagen was then used to fill the defects, and in two cases a Bio-Gide membrane was placed over the filled defect. Radiographs, clinical probing depths, and attachment levels were obtained before treatment and immediately preceding en bloc resection of teeth and surrounding tissues 9 months later. A mean pocket depth reduction of 5.75 mm and mean clinical attachment level gain of 5.25 mm were recorded. The histologic evaluation demonstrated the formation of a complete new attachment apparatus with new cementum, periodontal ligament, and alveolar bone at the level of and coronal to the calculus reference notch. Micro-CT evaluation confirmed the histologic results and demonstrated the absence of ankylosis or root resorption for all specimens. This human histologic study demonstrated that Bio-Oss Collagen has the capacity to facilitate regeneration of the periodontal attachment apparatus when placed in intrabony defects. Micro-CT observations confirmed the histologic results and enhanced the three-dimensional understanding of periodontal wound healing. The results indicate that micro-CT may be useful for three-dimensional evaluation of periodontal regenerative procedures.
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PMID:Three-dimensional micro-computed tomographic evaluation of periodontal regeneration: a human report of intrabony defects treated with Bio-Oss collagen. 1608 44

Collagen-induced arthritis (CIA) in mice is an experimental model for rheumatoid arthritis, a human chronic inflammatory destructive disease. The therapeutic effect of neutralizing the cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) by an antibody was examined in the mouse disease in a view of deriving a pharmacokinetic/pharmacodynamic (PKPD) model. In CIA mice the development of disease is measured by a total arthritic score (TAS) and an ankylosis score (AKS). We present a multi-response PKPD model which describes the time course of the unperturbed and perturbed TAS and AKS. The antibody acts directly on GM-CSF by binding to it. Therefore, a compartment for the cytokine GM-CSF is an essential component of the mathematical model. This compartment drives the disease development in the PKPD model. Different known properties of arthritis development in the CIA model are included in the PKPD model. Firstly, the inflammation, driven by GM-CSF, dominates at the beginning of the disease and decreases after some time. Secondly, a destructive (ankylosis) part evolves in the TAS that is delayed in time. In order to model these two properties a delay differential equation was used. The PKPD model was applied to different experiments with doses ranging from 0.1 to 100 mg/kg. The influence of the drug was modeled by a non-linear approach. The final mathematical model consists of three differential equations representing the compartments for GM-CSF, inflammation and destruction. Our mathematical model described well all available dosing schedules by a simultaneous fit. We also present an equivalent and easy reformulation as ordinary differential equation which grants the use of standard PKPD software.
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PMID:Multi-response model for rheumatoid arthritis based on delay differential equations in collagen-induced arthritic mice treated with an anti-GM-CSF antibody. 2219 31

The temporomandibular joint (TMJ) consists in the glenoid fossa arising from the otic capsule through intramembranous ossification, the fibrocartilaginous disc and the condyle, which is derived from the secondary cartilage by endochondral ossification. We have reported previously that cranial neural-crest-specific inactivation of the homeobox gene Shox2, which is expressed in the mesenchymal cells of the maxilla-mandibular junction and later in the progenitor cells and perichondrium of the developing chondyle, leads to dysplasia and ankylosis of the TMJ and that replacement of the mouse Shox2 with the human SHOX gene rescues the dysplastic and ankylosis phenotypes but results in a prematurely worn out articular disc. In this study, we investigate the molecular and cellular bases for the prematurely worn out articular disc in the TMJ of mice carrying the human SHOX replacement allele in the Shox2 locus (termed Shox2 (SHOX-KI/KI)). We find that the developmental process and expression of several key genes in the TMJ of Shox2 (SHOX-KI/KI) mice are similar to that of controls. However, the disc of the Shox2 (SHOX-KI/KI) TMJ exhibits a reduced level of Collagen I and Aggrecan, accompanied by increased activities of matrix metalloproteinases and a down-regulation of Ihh expression. Dramatically increased cell apoptosis in the disc was also observed. These combinatory cellular and molecular defects appear to contribute to the observed disc phenotype, suggesting that, although human SHOX can exert similar functions to mouse Shox2 in regulating early TMJ development, it apparently has a distinct function in the regulation of those molecules that are involved in tissue homeostasis.
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PMID:Replacing Shox2 with human SHOX leads to congenital disc degeneration of the temporomandibular joint in mice. 2424 41

Our previous study reported that inactivation of Shox2 led to dysplasia and ankylosis of the temporomandibular joint (TMJ), and that replacing Shox2 with human Shox partially rescued the phenotype with a prematurely worn out articular disc. However, the mechanisms of Shox2 activity in TMJ development remain to be elucidated. In this study, we investigated the molecular and cellular basis for the congenital dysplasia of TMJ in Wnt1-Cre; pMes-stop Shox2 mice. We found that condyle and glenoid fossa dysplasia occurs primarily in the second week after the birth. The dysplastic TMJ of Wnt1-Cre; pMes-stop Shox2 mice exhibits a loss of Collagen type I, Collagen type II, Ihh and Gli2. In situ zymography and immunohistochemistry further demonstrate an up-regulation of matrix metalloproteinases (MMPs), MMP9 and MMP13, accompanied by a significantly increased cell apoptosis. In addition, the cell proliferation and expressions of Sox9, Runx2 and Ihh are no different in the embryonic TMJ between the wild type and mutant mice. Our results show that overexpression of Shox2 leads to the loss of extracellular matrix and the increase of cell apoptosis in TMJ dysplasia by up-regulating MMPs and down-regulating the Ihh signaling pathway.
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PMID:Overexpression of Shox2 leads to congenital dysplasia of the temporomandibular joint in mice. 2506 48