Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tumour necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6) are potent inflammatory cytokines produced by osteoblasts and whose contribution to bone loss occurring in oestrogen deficiency is well documented. Calcitonin gene-related peptide (CGRP) is a neuropeptide abundantly concentrated in sensory nerve endings innervating bone metaphyses and periosteum suggesting that it controls bone homeostasis locally. Since CGRP was shown to inhibit TNF-alpha production by T cells and stimulate IL-6 expression by fibroblasts, this study was designed to investigate whether CGRP regulated TNF-alpha and IL-6 production by osteoblasts. We show that CGRP inhibits the production of TNF-alpha by both lipopolysaccharide (LPS)- and IL-1-stimulated fetal rat osteoblasts. Like CGRP, the cAMP agonists prostaglandin E2 (PGE2), dibutyryl cAMP (Bt2cAMP) and forskolin inhibit TNF-alpha production by osteoblasts. Exposure of osteoblasts to a high dose of phorbol myristoyl acetate (PMA) to deplete PKC activity abolished CGRP-mediated TNF-alpha suppression. In contrast with its potent inhibition of TNF-alpha production, we show that CGRP is a weak inducer of IL-6 when compared to PGE2, Bt2cAMP and forskolin. However, in presence of isobutylmethylxanthine (IBMX) CGRP stimulates the production of IL-6. Collectively, these data suggest that the inhibition of TNF-alpha CGRP is cAMP dependent and PMA sensitive and that the concentration of intracellular cAMP may be a regulatory mechanism for IL-6 expression in osteoblasts.
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PMID:The neuropeptide calcitonin gene-related peptide inhibits TNF-alpha but poorly induces IL-6 production by fetal rat osteoblasts. 941 11

Rapid and efficient animal models are needed for evaluating the effectiveness of many new candidate bone regenerative materials. We developed an in vivo model screening for calvarial bone regeneration in lipopolysaccharide (LPS)-treated mice, in which materials were overlaid on the periosteum of the calvaria in a 20 min surgery and results were detectable in 1 week. Intraperitoneal LPS injection reduced spontaneous bone formation, and local application of basic fibroblast growth factor (bFGF) increased the bone-forming activities of osteoblasts. A novel synthetic collagen gel, alkali-treated collagen (AlCol) cross-linked with trisuccinimidyl citrate (TSC), acted as a reservoir for basic substances such as bFGF. The AlCol-TSC gel in conjunction with bFGF activated osteoblast activity without the delay in osteoid maturation caused by bFGF administration alone. The AlCol-TSC gel may slow the release of bFGF to improve the imbalance between osteoid formation and bone mineralization. These findings suggest that our model is suitable for screening bone regenerative materials and that the AlCOl-TSC gel functions as a candidate reservoir for the slow release of bFGF.
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PMID:An in vivo murine model for screening cranial bone regenerative materials: testing of a novel synthetic collagen gel. 2457 57

This article reviews recent research into mechanisms underlying bone resorption and highlights avenues of investigation that may generate new therapies to combat alveolar bone loss in periodontitis. Several proteins, signaling pathways, stem cells, and dietary supplements are discussed as they relate to periodontal bone loss and regeneration. RGS12 is a crucial protein that mediates osteoclastogenesis and bone destruction, and a potential therapeutic target. RGS12 likely regulates osteoclast differentiation through regulating calcium influx to control the calcium oscillation-NFATc1 pathway. A working model for RGS10 and RGS12 in the regulation of Ca(2+) oscillations during osteoclast differentiation is proposed. Initiation of inflammation depends on host cell-microbe interactions, including the p38 mitogen-activated protein kinase (MAPK) signaling pathway. Oral p38 inhibitors reduced lipopolysaccharide (LPS)-induced bone destruction in a rat periodontitis model but showed unsatisfactory safety profiles. The p38 substrate MK2 is a more specific therapeutic target with potentially superior tolerability. Furthermore, MKP-1 shows anti-inflammatory activity, reducing inflammatory cytokine biosynthesis and bone resorption. Multipotent skeletal stem cell (SSC) populations exist within the bone marrow and periosteum of long bones. These bone-marrow-derived SSCs and periosteum-derived SSCs have shown therapeutic potential in several applications, including bone and periodontal regeneration. The existence of craniofacial bone-specific SSCs is suggested based on existing studies. The effects of calcium, vitamin D, and soy isoflavone supplementation on alveolar and skeletal bone loss in post-menopausal women were investigated. Supplementation resulted in stabilization of forearm bone mass density and a reduced rate of alveolar bone loss over 1 yr, compared with placebo. Periodontal attachment levels were also well-maintained and alveolar bone loss suppressed during 24 wk of supplementation.
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PMID:Alveolar bone loss: mechanisms, potential therapeutic targets, and interventions. 2473 3