PubMed · 1087764
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H Schmidt. 1976. [An interesting case].. https://pubmed.ncbi.nlm.nih.gov/1087764/
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Bone resorption is commonly associated with aging and with certain types of cancer, including multiple myeloma and breast cancer. What induces bone resorption is not fully understood, but the role of osteoclasts is well established. Recently, receptor activator of nuclear factor-kappaB (NF-kappaB) ligand (RANKL), a member of the tumor necrosis factor superfamily, was implicated as a major mediator of bone resorption, suggesting that agents that can suppress RANKL signaling have the potential to inhibit bone resorption or osteoclastogenesis. Guggulsterone [4,17(20)-pregnadiene-3,16-dione], isolated from the guggul tree Commiphora mukul and used to treat osteoarthritis and bone fractures, was recently shown to antagonize the farnesoid X receptor, decrease the expression of bile acid-activated genes, and suppress the NF-kappaB activation induced by various carcinogens. We investigated whether guggulsterone could modulate RANKL signaling and osteoclastogenesis induced by RANKL or tumor cells. We found that treatment of monocytes with guggulsterone suppressed RANKL-activated NF-kappaB activation (as indicated by gel-shift assay) and that this suppression correlated with inhibition of IkappaBalpha kinase and phosphorylation and degradation of IkappaBalpha, an inhibitor of NF-kappaB. Guggulsterone also suppressed the differentiation of monocytes to osteoclasts in a dose-dependent and time-dependent manner. Suppression of osteoclastogenesis by the NF-kappaB-specific inhibitory peptide implies a link between NF-kappaB and osteoclastogenesis. Finally, differentiation to osteoclasts induced by coincubating human breast tumor cells (MDA-MB-468) or human multiple myeloma (U266) cells with monocytes was also completely suppressed by guggulsterone. Collectively, our results indicate that guggulsterone suppresses RANKL and tumor cell-induced osteoclastogenesis by suppressing the activation of NF-kappaB.
BACKGROUND: A connection of herpesvirus periapical infection with symptomatic and large-size periapical lesions has been recognized in adult patients, but no data exist about a possible involvement of herpesviruses in severe periapical pathosis in children. Herpesviruses have the potential to elicit potent bone resorption-inducing cytokines in mammalian cells. AIM: This study aimed to determine the occurrence of human cytomegalovirus and Epstein-Barr virus DNA, and mRNA transcripts of receptor activator of nuclear kappa B ligand (RANKL), osteoprotegerin, core binding factor alpha-1, colony stimulating factor-1, transforming growth factor-beta, and monocyte chemoattractant protein-1 in periapical symptomatic pathosis of deciduous teeth. MATERIAL AND METHODS: Twelve deciduous molar teeth from patients aged 2-8 years were extracted due to severe periapical infection, and granulomatous tissue adherent to the root tip of the extracted teeth was collected using a surgical knife. Non-diseased pulpal tissue, obtained from 12 teeth extracted for orthodontic reasons, served as negative control. Polymerase chain reaction assays were employed to identify herpesvirus DNA and cytokine gene expression, using established polymerase chain reaction primers and procedures. RESULTS: Seven (58%) of the periapical lesions yielded human cytomegalovirus and eight (67%) Epstein-Barr virus. Only one (8%) periapical lesion showed neither human cytomegalovirus nor Epstein-Barr virus. In healthy pulpal tissue, one (8%) specimen demonstrated human cytomegalovirus and another (8%) specimen revealed Epstein-Barr virus. Of the cytokines examined, RANKL expression showed significantly higher occurrence in periapical pathosis than in healthy pulpal tissue (P < 0.040). No relationship was identified between the type of herpesvirus and cytokine expression in the periapical lesions studied. CONCLUSIONS: The present findings provide evidence of a putative role of human cytomegalovirus and Epstein-Barr virus in the pathogenesis of symptomatic periapical pathosis in deciduous teeth. Increased RANKL expression in periapical lesions may be of pathogenetic significance.
Drug-induced hypercalcemia is caused by increased bone resorption (vitamin D and vitamin A intoxication), increased calcium absorption in the gastrointestinal tract (vitamin D intoxication, excessive intake of calcium) or increased calcium reabsorption in the renal tubules (thiazide diuretics). When vitamin D (D(2) or D(3)) intoxication develops, the hypercalcemia persists for more than several months. Therefore, short-acting active vitamin D (1alpha-OHD(3), 1,25- (OH) (2)D(3)) are clinically used. Recently, various analogs of 1,25- (OH) (2)D(3) with potent differentiation stimulating activity on keratinocytes but insufficient calcium-movilizing activity have been developed (tacalcitol, calcipotriol, 22-oxacalcitriol). However, severe hypercalcemia may develop when these ointments were abundantly applied to patients with psoriasis since the agents can be easily absorbed through the skin lesions.