Osteopontin deficiency suppresses high phosphate load-induced bone loss via specific modulation of osteoclasts

Phosphate (Pi) plays a critical role in the maintenance of mineralized tissues and signaling in the intracellular environment. Although extracellular phosphate concentration is maintained at fixed levels, physiological machineries involved in phosphate homeostasis in bone, which is the largest phosphate storage site, have not yet been fully elucidated. Here we examined the role of osteopontin (OPN) in a high-Pi diet load-induced bone loss. A high-Pi diet significantly reduced bone mineral density as well as bone mass in wild type. In contrast, OPN deficiency totally prevented reduction in bone mineral density and bone mass. Analyses of bone turnover-related components revealed that bone formation parameters (bone formation rate and mineral apposition rate) were enhanced by high-Pi diet load similarly in wild-type and OPN-deficient mice. In sharp contrast, bone resorption parameters (osteoclast number and osteoclast surface) were enhanced by high-Pi diet load in wild type but not at all in OPN-deficient mice. Bone marrow cell cultures revealed no major effects of OPN deficiency on high-Pi diet modulation of mineralized nodule formation in culture. On the other hand, tartrate-resistant acid phosphatase-positive multinucleated cell development in cultures were enhanced by high-Pi diet load in wild-type cells, but such effects of high Pi-diet were totally abolished in the absence of OPN. These data indicated that OPN is needed for osteoclastic activity to resorb bone on high phosphate loading.     

Influence of Adjuncts to Irrigation in the Disinfection of Large Root Canals

Introduction

The aims of this study were to evaluate the effectiveness of disinfection methods and determine the most promising irrigation protocol for regenerative endodontics in teeth with large root canals.

Biological activity of Anthraquinones and Triterpenoids from Prismatomeris fragrans

A new 1,3-dihydroxy-2-methyl-5,6-dimethoxyanthraquinone (1); six known anthraquinones, nordamnacanthal (2), damnacanthal (3), rubiadin (4), rubiadin-1-methyl ether (5), lucidin-ω-methyl ether (6), and 1-hydroxy-2-hydroxymethyl-3-methoxyanthraquinone (7); a β-sitosterol (8); together with two known triterpenoids, β-acetylolean-12-en-28-olic acid (9), and 3β-O-acetyl-11,12-epoxyolean-28,13-olide (10) were isolated from the roots and stems of Prismatomeris fragrans. Their structures were established on the basis of spectral data. This is the first isolation of compounds 2, 6, 7, 9 and 10 from Prismatomeris genus. The isolated compounds were evaluated in antiplasmodial, antituberculosis, antifungal and anticancer cell lines tests. The bioactivity assays showed that only 9 exhibited moderate antimalarial activity, 2 and 3 exhibited antifungal activity while 2, 3, 4, 7 and 9 showed antituberculosis activity. In addition, compounds 2, 3 and 7 exhibited cytotoxicity to BC cell line while 1, 1a (the methyl ether derivative of 1), 2, 3, 4, 5, and 9 exhibited cytotoxicity to NCI-H187 cell line.     

Runx2 is a target of mechanical unloading to alter osteoblastic activity and bone formation in vivo

Molecular mechanisms underlying unloading-induced reduction of bone formation have not yet been fully understood. In vitro, Runx2 has been suggested to be involved in mechanical signaling in osteoblasts. However, the roles of Runx2 in vivo during the bone response to mechanical stimuli have not yet been known. The purpose of this paper was to examine the roles of Runx2 in unloading-induced bone loss in vivo. Tail suspension was conducted for 2 wk using 9- to 11-wk-old Runx2 heterozygous knockout mice (Runx2(+/-)) and wild-type (Wt) littermates. Bones were subjected to two-dimensional micro-x-ray computed tomography, bone histomorphometry and RT-PCR analyses. Loss of half Runx2 gene dosage-exacerbated unloading-induced bone loss in trabecular and cortical envelopes. Unloading-induced reduction in mineral apposition rate and bone formation rate in cortical bone as well as trabecular bone was exacerbated in Runx2(+/-) mice, compared with Wt mice. Bone resorption parameters were not significantly affected by unloading or Runx2(+/-) genotype. Basal Runx2 and osterix mRNA levels in bone were reduced by 50% in Wt, whereas unloading in Runx2(+/-) mice did not further alter Runx2 and osterix mRNA levels. In contrast, osteocalcin mRNA levels were reduced by unloading, regardless of Runx2 gene dosage. These data demonstrated that full Runx2 gene dosage is required for maintaining normal function of osteoblasts in mechanical unloading or nonphysiological condition. Finally, we propose Runx2 as a critical target gene in unloading to alter osteoblastic activity and bone formation in vivo.