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

The presence of cholesterol crystals has been suggested to be a factor interfering with periapical healing after conventional endodontic treatment. This investigation addresses the role of cholesterol crystals in impairing healing by studying the tissue response to the crystals, which were implanted in animals. Pure cholesterol crystals, prepared to a mushy form, were placed in Teflon cages that were implanted subcutaneously in guinea pigs. The cage-contents were retrieved after 2, 4 and 32 wk of implantation and processed for light and electron microscopy. The cages revealed delicate connective tissue that grew in through perforations on the cage-wall. The crystals were densely surrounded by numerous macrophages and multinucleated giant cells, forming a well-circumscribed area of tissue reaction. The cells, however, were unable to eliminate the crystals during an observation period of 8 months. The congregation of macrophages and giant cells, known to be major sources of apical inflammatory and bone resorptive mediators, suggest that accumulation of cholesterol crystals can be a factor in the failure of certain apical periodontitis lesions to resolve after conventional root-filling therapy.
...
PMID:Cholesterol crystals as an etiological factor in non-resolving chronic inflammation: an experimental study in guinea pigs. 958 11

Prevotella intermedia is a major periodontopathogen contributing to human gingivitis and periodontitis. Such pathogens release proteases as virulence factors that cause deterrence of host defenses and tissue destruction. A new cysteine protease from the cysteine-histidine-dyad class, interpain A, was studied in its zymogenic and self-processed mature forms. The latter consists of a bivalved moiety made up by two subdomains. In the structure of a catalytic cysteine-to-alanine zymogen variant, the right subdomain interacts with an unusual prodomain, thus contributing to latency. Unlike the catalytic cysteine residue, already in its competent conformation in the zymogen, the catalytic histidine is swung out from its active conformation and trapped in a cage shaped by a backing helix, a zymogenic hairpin, and a latency flap in the zymogen. Dramatic rearrangement of up to 20A of these elements triggered by a tryptophan switch occurs during activation and accounts for a new activation mechanism for proteolytic enzymes. These findings can be extrapolated to related potentially pathogenic cysteine proteases such as Streprococcus pyogenes SpeB and Porphyromonas gingivalis periodontain.
...
PMID:A new autocatalytic activation mechanism for cysteine proteases revealed by Prevotella intermedia interpain A. 1799 55

Periodontitis is affecting over half of the adult population, and represents a major public health problem. Previously, we isolated a subset of gingival fibroblasts (GFs) from periodontitis patients, designated as periodontitis-associated fibroblasts (PAFs), which were highly capable of collagen degradation. To elucidate their molecular profiles, GFs isolated form healthy and periodontitis-affected gingival tissues were analyzed by CAGE-seq and integrated with the FANTOM5 atlas. GFs from healthy gingival tissues displayed distinctive patterns of CAGE profiles as compared to fibroblasts from other organ sites and characterized by specific expression of developmentally important transcription factors such as BARX1, PAX9, LHX8, and DLX5. In addition, a novel long non-coding RNA associated with LHX8 was described. Furthermore, we identified DLX5 regulating expression of the long variant of RUNX2 transcript, which was specifically active in GFs but not in their periodontitis-affected counterparts. Knockdown of these factors in GFs resulted in altered expression of extracellular matrix (ECM) components. These results indicate activation of DLX5 and RUNX2 via its distal promoter represents a unique feature of GFs, and is important for ECM regulation. Down-regulation of these transcription factors in PAFs could be associated with their property to degrade collagen, which may impact on the process of periodontitis.
...
PMID:Transcriptome analysis of periodontitis-associated fibroblasts by CAGE sequencing identified DLX5 and RUNX2 long variant as novel regulators involved in periodontitis. 2764 61