Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0031099 (periodontitis)
12,489 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The pharmacological effect of hydroxyapatite and a composition based on it in the form of Stimulos sponge has been studied in human osteogenic tissue culture. Hydroxyapatite stimulated the biosynthetic processes in the cells. Addition of chlorohexidine and thymogen to the composition in order to increase its antibacterial activity did not decrease the osteoinductive properties of the drug. Trials of Stimulos in 66 patients with chronic generalized periodontitis demonstrated its high efficacy, particularly of the compositions containing immunostimulants: inflammation disappeared and the height of alveolar osseous tissue increased, as did bone compactness.
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PMID:[A clinical and experimental validation of the use of Stimuloss in patients with chronic generalized periodontitis]. 924 1

Regeneration of damaged periodontal tissues is mediated by periodontal cells, but a major sub-population comprises highly differentiated cells that do not renew. To overcome the loss of specialized cell types caused by disease, various therapeutic approaches including cell transplants have been developed to promote cell re-population in periodontal tissues. As previous transplantation studies used unlabeled cells, that are indistinguishable from host cells, it has been difficult to assess the contributions of transplanted cells to the healing processes. To track the fate and differentiation of rat periodontal cells transplanted into periodontal wounds, we used collagen-coated fluorescent beads as a permanent endocytosed marker, or cells constitutively expressing beta-galactosidase. We assessed osteogenic cell differentiation with immunohistochemical staining for osteopontin and bone sialoprotein. Cells were transplanted into periodontal wounds created in Sprague--Dawley male rats that are null for beta-galactosidase. Defects were allowed to heal spontaneously (controls), or were closed with collagen implants mixed with beta-galactosidase-positive (Lac-Z) periodontal cells, or closed with collagen implants mixed with periodontal cells loaded with fluorescent beads. Animals were killed at 1 and 2 weeks after surgery and tissues were prepared for morphometric assessment and immunostaining for osteopontin (OPN) and bone sialoprotein (BSP). Transplanted cells were easily distinguished by fluorescent beads or by beta-galactosidase-positive expression and were distributed throughout the regenerating periodontal ligament (PL) and alveolar bone. At 1 week after wounding, animals treated with beta-galactosidase-positive cells exhibited a slightly higher percentage of labeled cells in the PL compared with the fluorescent bead-labeled cell implant group (2% vs. 1% respectively; P > 0.2). At Week 2 percentages of labeled cells were slightly increased in the regenerating PL (approximately 3% for both groups, P > 0.2). In regenerating alveolar bone at 1 week, animals that were treated with beta-galactosidase-positive cells and fluorescent bead-loaded cells exhibited approximately 30% and 25% of labeled cells respectively. At 2 weeks after wounding there was an increase in the percentage of transplanted beta-galactosidase-positive cells (approximately 39% at week 2; P < 0.05), but not of transplanted cells with fluorescent beads (approximately 25% at week 2). In sites with transplanted cells there were higher percentages of OPN positive and BSP positive cells in nascent bone and more newly formed bone than in controls (>40%; P < 0.05). Transplantation of beta-galactosidase-positive cells or cells loaded with fluorescent beads is a useful method for assessing the fate and differentiation of periodontal cells in vivo. Fluorescent beads, however, are diluted at mitosis and this method underestimates the percentage of transplanted cells. As transplanted periodontal cells in both groups promoted regeneration of alveolar bone, cell transplantation could improve the restoration of periodontium destroyed by periodontitis.
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PMID:Transplantation of labeled periodontal ligament cells promotes regeneration of alveolar bone. 1116 14

Regenerative medicine, which takes advantage of the unique capacity of stem cells, is a novel medical strategy to cure irreversible organ failure. There are three important elements in regenerative medicine: cells, scaffolds and signals. Although substantial progress regarding each element has been made in the past few years, it still falls short of clinical applications. In the geriatric field, osteoporosis, osteoarthritis and periodontitis are the major targets of regenerative medicine. They are usually not life-threatening, but often severely affect QOL of elderly patients. Since elderly people have already reduced number of stem cells in bone and cartilage, we need to know the sufficient conditions for osteogenesis and chondrogenesis by comprehensively screening various conditions. We developed a marker gene system expressing green fluorescence protein (GFP) under the control of osteoblast- and chondrocyte-specific promoters. This system helps us monitor osteoblast and chondrocyte differentiation easily, precisely and non-invasively. Using this system, we are now trying to find the sufficient conditions for osteogenesis and chondrogenesis, and to discover osteogenic and chondrogenic small compounds.
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PMID:[Regenerative medicine of bone and cartilage]. 1565 65

Recent studies have shown the biological and clinical significance of signaling pathways of osteogenic cytokines RANKL-RANK/OPG in controlling osteoclastogenesis associated with bone pathologies, including rheumatoid arthritis, osteoporosis, and other osteolytic disorders. In contrast to the inhibitory effect of gamma interferon (IFN-gamma) on RANKL-mediated osteoclastogenesis reported recently, alternative new evidence is demonstrated via studies of experimental periodontitis using humanized NOD/SCID and diabetic NOD mice and clinical human T-cell isolates from diseased periodontal tissues, where the presence of increasing IFN-gamma is clearly associated with (i) enhanced Actinobacillus actinomycetemcomitans-specific RANKL-expressing CD4(+) Th cell-mediated alveolar bone loss during the progression of periodontal disease and (ii) a concomitant and significantly increased coexpression of IFN-gamma in RANKL(+) CD4(+) Th cells. Therefore, there are more complex networks in regulating RANKL-RANK/OPG signaling pathways for osteoclastogenesis in vivo than have been suggested to date.
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PMID:Gamma interferon positively modulates Actinobacillus actinomycetemcomitans-specific RANKL+ CD4+ Th-cell-mediated alveolar bone destruction in vivo. 1590 74

A derivative (EMD) of enamel matrix proteins (EMPs) is used for periodontal regeneration because EMPs are believed to induce the formation of acellular extrinsic fiber cementum (AEFC). Other reports, however, indicate that EMPs have osteogenic potential. The aim of this study was to characterize the nature of the tissue that forms on the root surface following application of EMD. Ten human teeth affected by periodontitis and scheduled for extraction were treated with EMD. Four to six weeks later, they were extracted and processed for analysis by light microscopy and transmission electron microscopy. Immunocytochemistry with antibodies against bone sialoprotein (BSP) and osteopontin (OPN) was performed to determine the mineralization pattern. The newly formed tissues on the root were thick and contained embedded cells. Small mineralization foci were regularly seen, and large organic matrix patches were occasionally seen, but a distinct mineralization front was lacking. While labeling for BSP was always associated with small mineralization foci and large matrix patches, OPN labeling was seen inconsistently. It is concluded that tissues resembling either cellular intrinsic fiber cementum or a type of bone were observed. The mineralization pattern mostly resembled that found in bone, except for a few areas that exhibited a hitherto undescribed mineralization pattern.
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PMID:Pattern of mineralization after regenerative periodontal therapy with enamel matrix proteins. 1667 90

In this work, we examined the culture condition of alveolar bone marrow multipotent mesenchymal stromal cells (ABMMSCs), aiming to apply regenerative therapy to older periodontitis patients. To better understand the character of cultured cells from alveolar bone marrow, the expression profiles of well-known genes and their responses to the induction of osteogenic, chondrogenic, or adipogenic differentiation were examined. Using alpha MEM-based culture, ABMMSCs could be obtained from older individuals than in previous reports. Interestingly, ABMMSCs expressing Klf4 were able to differentiate into osteoblasts. The prediction of differentiation potential by Klf4 could be a useful guide for further improvement of the culture conditions required to culture ABMMSCs derived from older individuals.
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PMID:Collection and culture of alveolar bone marrow multipotent mesenchymal stromal cells from older individuals. 1950 74

'Bone: Formation by autoinduction', initiates by invocation of soluble molecular signals which, when combined to insoluble signals or substrata trigger the ripple-like cascade of bone differentiation by induction. The osteogenic proteins of the transforming growth factor-beta (TGF-beta) superfamily, the bone morphogenetic/osteogenic proteins (BMPs/OPs), and uniquely in the non-human primate Papio ursinus also the three mammalian TGF-beta isoforms, induce endochondral bone formation as recapitulation of embryonic development. The pleiotropic activities of the BMPs/OPs are vast and include the induction of periodontal tissue regeneration. Implantation of naturally derived highly purified osteogenic fractions after sequential adsorption/affinity and gel filtration chromatography in mandibular Class II furcation defects of P. ursinus induces cementogenesis as highly cellular collagenic cementoid attached to the exposed dentine with foci of nascent mineralization with inserted de novo generated Sharpey's fibres. Recombinant human osteogenic protein-1 (hOP-1) when implanted in Class II furcation defects of P. ursinus with surgically exposed dentine matrix preferentially initiates the induction of cementogenesis; on the other hand, hBMP-2 preferentially induces alveolar bone regeneration with mineralized bone covered by prominent osteoid seams. Long-term studies with gamma-irradiated 0.5 and 2.5mg hOP-1 per gram of xenogeneic bovine collagenous matrix induce the restitutio ad integrum of the periodontal tissues in furcation defects exposed by chronic periodontitis in P. ursinus. A challenging question for tissue engineering and regenerative medicine is whether the presence of molecularly different osteogenic proteins of the TGF-beta superfamily has a therapeutic significance. Mechanistically, the specificity of hOP-1 primarily initiating cementogenesis in periodontal defects is regulated by both the dentine extracellular matrix upon which responding cells attach and differentiate, and the structure/activity profile of the implanted hOP-1; the limited induction of cementogenesis by hBMP-2 in furcation defects of non-human primate and canine models is consistent with the reported data that hBMP-2 inhibits differentiation and mineralization of cementoblasts in vitro aside the specific structure/activity profile of the implanted hBMP-2 protein. The induction of periodontal tissue regeneration develops as a mosaic structure in which the osteogenic proteins of the TGF-beta superfamily singly, synergistically and synchronously initiate and maintain tissue induction and morphogenesis as a recapitulation of embryonic development.
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PMID:Bone morphogenetic proteins, cementogenesis, myoblastic stem cells and the induction of periodontal tissue regeneration. 1989 1

Osteogenic cells have been found within periosteal tissue. Periosteal cells will also form a membranous structure under the appropriate culture conditions. We have characterized the osteogenic potential of this membranous cultured periosteum (CP) and have demonstrated that CP can successfully regenerate alveolar bone defects in a canine periodontitis model. The aim of this study is to demonstrate periodontal tissue regeneration by using CP for patients with severe periodontitis. CP was applied in treatments for severe alveolar bone defects for a total of seven teeth among four periodontitis patients. Bone formation was evaluated by dental radiography 4 months after grafting, with a follow-up period of 12 to 15 months. CP was successfully generated and formed a membrane (approximately 4 cm in diameter) about 4 weeks after attachment to the dish. Vertical bone gain (3 to 8 mm) was observed in all grafted areas at 4 months post-surgery. The probing depth was also reduced to its normal depth and remained so beyond one year. Results from the present cases suggest that periodontitis patients with bone defects can benefit from CP treatment. Post-operative evaluation indicates periodontal tissue regeneration after CP treatment, suggesting a broad application for patients with periodontal disease.
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PMID:Efficacy of membranous cultured periosteum for the treatment of patients with severe periodontitis: a proof-of-concept study. 2022 4

Periodontal ligament (PDL) can be obtained from patients undergoing orthodontic treatment. PDL contains progenitor cells that can be expanded and differentiated towards several mesenchymal lineages in vitro. Furthermore, PDL-derived cells have been shown to generate bone- and PDL-like structures in vivo. Thus, PDL cells, combined with suitable biomaterials, represent a promising tool for periodontitis-related research and PDL engineering. Here, a new PDL cell line using lentiviral gene transfer of human telomerase reverse transcriptase (hTERT) was created. HTERT-expressing PDL cells showed similar morphology and population doubling time but an extended lifespan compared to the primary cells. In addition, PDL-hTERT cells expressed several characteristic genes and upon osteogenic stimulation produced a calcified matrix in vitro. When cultivated on two topographically different titanium scaffolds (MA and SLA), PDL-hTERT cells exhibited augmented spreading, survival and differentiation on smooth (MA) compared to rough (SLA) surfaces. These findings differ from previously reported osteoblast behaviour, but they are in agreement with the behaviour of chondrocytes and gingival fibroblasts, suggesting a very cell type-specific response to different surface textures. In summary, we report the testing of titanium biomaterials using a new PDL-hTERT cell line and propose this cell line as a useful model system for periodontitis research and development of novel strategies for PDL engineering.
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PMID:Establishment of immortalized periodontal ligament progenitor cell line and its behavioural analysis on smooth and rough titanium surface. 2047 31

Chronic inflammatory diseases, such as rheumatoid arthritis and periodontitis, are the most common causes of bone tissue destruction. Recently, human periodontal ligament tissue-derived mesenchymal stem cells (PDLSCs), a population of multipotent stem cells, have been used to reconstruct tissues destroyed by chronic inflammation. However, the impact of the local inflammatory microenvironment on tissue-specific stem cells and the mechanisms controlling the effects of the local inflammatory environment remain poorly understood. In this study, we found that the multidifferentiation potential of mesenchymal stem cells (MSCs) isolated from periodontitis-affected periodontal ligament tissue (P-PDLSCs) was significantly lower than that of MSCs isolated from healthy human periodontal ligament tissue (H-PDLSCs). Inflammation in the microenvironment resulted in an inhibition of miR-17 levels, and a perturbation in the expression of miR-17 partly reversed the differentiation potential of PDLSCs in this microenvironment. Furthermore, inflammation in the microenvironment promoted the expression of Smad ubiquitin regulatory factor one (Smurf1), an important negative regulator of MSC osteogenic differentiation. Western blotting and 3' untranslated regions (3'-UTR) reporter assays confirmed that Smurf1 is a direct target of miR-17 in PDLSCs. Our data demonstrate that excessive inflammatory cytokine levels, miR-17, and Smurf1 were all involved in a coherent feed-forward loop. In this circuit, inflammatory cytokines led to direct activation of Smurf1 and downregulation of miR-17, thereby increasing degradation of Smurf1-mediated osteoblast-specific factors. The elucidation of the molecular mechanisms governing MSC osteogenic differentiation in a chronic inflammatory microenvironment could provide us with a better knowledge of chronic inflammatory disorder and improve stem cell-mediated inflammatory bone disease therapy.
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PMID:MiR-17 modulates osteogenic differentiation through a coherent feed-forward loop in mesenchymal stem cells isolated from periodontal ligaments of patients with periodontitis. 2189 95


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