A naturally occurring rare analog of quercetin promotes peak bone mass achievement and exerts anabolic effect on osteoporotic bone.

UNLABELLED: The effect of quercetin C-glucoside (QCG) on osteoblast function in vitro and bone formation in vivo was investigated. QCG supplementation promoted peak bone mass achievement in growing rats and new bone formation in osteopenic rats. QCG has substantial oral bioavailability. Findings suggest a significant bone anabolic effect of QCG. INTRODUCTION: Recently, we showed that extracts of Ulmus wallichiana promoted peak bone mass achievement in growing rats and preserved trabecular bone mass and cortical bone strength in ovariectomized (OVx) rats. 3,3',4',5,7-Pentahydroxyflavone-6-C-ß-D-glucopyranoside, a QCG, is the most abundant bioactive compound of U. wallichiana extract. We hypothesize that QCG exerts bone anabolic effects by stimulating osteoblast function. METHODS: Osteoblast cultures were harvested from rat calvaria and bone marrow (BM) to study differentiation and mineralization. In vivo, growing female Sprague Dawley rats and OVx rats with osteopenia were administered QCG (5.0 or 10.0 mg kg(-1) day(-1)) orally for 12 weeks. Efficacy was evaluated by examining changes in bone microarchitecture using histomorphometric and microcomputed tomographic analyses and by determination of new bone formation by fluorescent labeling of bone. Plasma and BM levels of QCG were determined by high-performance liquid chromatography. RESULTS: QCG was much more potent than quercetin (Q) in stimulating osteoblast differentiation, and the effect of QCG was not mediated by estrogen receptors. In growing rats, QCG increased BM osteoprogenitors, bone mineral density, bone formation rate, and cortical deposition. In osteopenic rats, QCG treatment increased bone formation rate and improved trabecular microarchitecture. Comparison with the sham group (ovary intact) revealed significant restoration of trabecular bone in osteopenic rats treated with QCG. QCG levels in the BM were ~50% of that of the plasma levels. CONCLUSION: QCG stimulated modeling-directed bone accrual and exerted anabolic effects on osteopenic rats by direct stimulatory effect on osteoprogenitors likely due to substantial QCG delivery at tissue level following oral administration.

Role of calcium-sensing receptor in bone biology.

Bone turnover helps accomplish long-term correction of the extracellular calcium (Ca2+ o) homeostasis by the actions of osteoblasts and osteoclasts. These processes are highly regulated by the actions of hormones, most prominently parathyroid hormone (PTH), the release of which is a function of the Ca2+ o, and is regulated by the action of the Ca2+ -sensing receptor (CaR) in the parathyroid gland. Various mutations of the CaR gene give rise to gain or loss of functions leading respectively to hypo- or hypercalcaemic conditions. CaR could conceivably be a target for local changes in the Ca2+ o in the bone microenvironment thereby acting as a 'growth factor' in various cells residing in the bone marrow. This review discusses about the roles of the CaR in bone. In osteoblasts, CaR promotes its proliferation, differentiation and mineralization. In osteoclasts, CaR mediates high Ca2+ o-stimulated osteoclast differentiation as well as osteoclast apoptosis. CaR regulates localization of haematopoietic stem cells from the foetal liver to endosteal niche, the socalled homing. Although the CaR plays a key role in the defense against hypercalcaemia, its function can be aberrant in humoral hypercalcaemia of malignancy in which CaR activation stimulates secretion of parathyroid hormone-related peptide (PTHrP) secretion. Increased levels of PTHrP cause a vicious hypercalcaemic state resulting from its increased bone-resorptive and positive renal calcium reabsorbing effects give rise to hypercalcaemia. CaR mediates a variety of functions of Ca2+ o in the bone microenvironment under both normal and pathological conditions.

Monitoring of anti-HLA and anti-Major histocompatibility complex class I related chain A antibodies in living related renal donor transplantation.

This study was undertaken with the aim to analyze the clinical relevance of posttransplant anti-HLA and anti-major histocompatibility complex class I related chain A (MICA) antibodies in response to living related donor renal transplantation. A total of 185 consecutive post-renal transplant recipient serum samples were analyzed for the detection of anti-HLA and MICA antibodies using enzyme-linked immunosolvent assay techniques. Patients carrying both anti-HLA as well as anti-MICA antibodies (MICA(+)/HLA(+)) were the worst affected, showing significantly poorer graft survival compared with the MICA-/HLA-negative group (17% vs 89%, chi(2) = 19.63, P = .000). Similarly, patients with only MICA antibodies or those with only HLA antibodies also had significantly lower graft survival (P = .035 and P = .001, respectively) as compared to the nonsensitized group. The study illustrated that posttransplant monitoring antibodies to both MICA as well as HLA could be good predictors of renal allograft failure.

Allosensitization to HLA and MICA is an important measure of renal graft outcome.

The objective of this study was to evaluate the donor-specific antibody repertoire against T and B cells and monocytes, as well as the non-donor anti-HLA, and MICA (MHC class I-related chain A) antibodies in recipients of the live related donor renal transplantation. Sera collected before and after transplantation were tested by ELISA for the presence of HLA class I- and class II-specific antibodies and by Luminex MICA single-antigen bead assay for the detection of MICA antibodies. Patients having a combination of both anti-HLA and MICA antibodies had worse graft survival and more rejection episodes as compared to the group without antibodies. Further, presence of IgG antibodies against the donor cells (T, B & monocytes) led to a compromised graft survival along with higher incidence of acute rejection as compared to the negative groups. These results suggest that a comprehensive assessment of anti-donor antibody repertoire and monitoring of anti-HLA, MICA antibodies following transplantation is a useful exercise to detect the sensitization status of the recipient and this can prove to be of immense prognostic value in renal transplantation.

Purification and characterization of histamine dehydrogenase from Nocardioides simplex IFO 12069.

Histamine dehydrogenase from Nocardioides simplex IFO 12069 was purified to homogeneity. The enzyme had a molecular mass of 170 kDa and was suggested to be a dimer of subunits that had a molecular mass of 84 kDa. The enzyme showed highest activity toward histamine and produced ammonia in its oxidative deamination to imidazole acetaldehyde. The K(m) and V(max) values for histamine were 0.075 mM and 4.76 micromol min(-1) mg(-1), respectively. The enzyme was sensitive to the carbonyl reagent iproniazid and a structurally similar compound, tryptophan. The enzyme showed absorption maxima at 442 and 280 nm. Reduction with histamine under anaerobic conditions resulted in a different absorption maximum at 360 nm instead of 442 nm. The enzyme was most active at pH 8.5 in Tris-HCl buffer and most stable at pH 7.0 in potassium phosphate buffer. The E(1%) value of the enzyme was 8.6 at 280 nm.

Mineral and parathyroid hormone inter-relationships in normal pregnancy and pregnancy-induced hypertension.

The serum of calcium, other involved minerals and parathyroid hormone (PTH) were studied in non-pregnant women, during pregnancy and in pregnancy-induced hypertension (PIH). In pregnant women, serum creatinine, total calcium, total protein, albumin, inorganic phosphorus and magnesium declined, while parathyroid hormone levels increased significantly when compared to non-pregnant women. In PIH cases, serum total proteins, albumin and inorganic phosphorus were further reduced, while PTH levels were further increased when compared to normal pregnant women. Serum ionised calcium and sodium levels were similar in all the three groups. No significant relationship between blood pressure, PTH and involved minerals was observed in this study.