The changes on the regional distributions and frequencies of two types of chromogranin, chromogranin A (CGA) and bovine Sp-1 chromogranin (BCG)-immunoreactive (IR)cells in gastrointestinal (GI)tract of osteoporotic Sprague-Dawley rat induced by ovariectomy were studied by immunohistochemical methods. The experimental animals were divided into two groups, one is non-ovariectomized group (Sham)and the other is ovariectomized group (OVX). Samples were collected from each part of GI tract at 10th week after ovariectomy or sham operation. CGA-IR cells were restricted to the stomach regions with various frequencies regardless of ovariectomy except for the fundus of OVX in which no cells were detected. In addition, BCG-IR cells were also restricted to the pylorus and duodenum regardless of ovariectomy. A significantly decrease of CGA IR cells was detected in OVX compared to that of Sham in both fundus and pylorus, and BCG-IR cells were also significantly decreased in the duodenum(p<0. 05). However, in the pylorus, BCG-IR cells in OVX showed similar frequency compared to that of Sham. In conclusion, the abnormality in density of chromogranin, a generally used GI endocrine cell marker, detected in this study may contribute to the development of GI symptoms in osteoporosis such as impairments of calcium and some lipids, frequently encountered in patients with postmenopausal osteoporosis.
Animals ; Chromogranin A ; Chromogranins/*metabolism ; Female ; Gastric Mucosa/*metabolism/pathology ; Gene Expression Regulation/physiology ; Humans ; Immunoglobulins/*metabolism ; Immunohistochemistry ; Intestinal Mucosa/*metabolism/pathology ; Models, Animal ; Osteoporosis, Postmenopausal/*metabolism/pathology ; Ovariectomy ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo study the regulation of hypoxia inducible factor-1alpha (HIF-1alpha) on osteoblast function in postmenopausal osteoporosis.

METHODSFrom October 2004 to May 2006, Cre-Loxp recombinase was used to create mice which the HIF-1alpha gene in osteoblasts was conditional knock-out, 24 female wild-type (WT) mice and 24 female conditional knock-out (CKO) mice of 3 months old were operated on ovariotomy. At 0,4,8 weeks after operation, bone histomorphometry parameters were measured with computer image analysis in HE stain sections and in tetracycline bone double labeling fluorescence sections; Bone density and the trabecular bone architecture parameters were measured by Micro-CT; The mRNA expression of vascular endothelial growth factors (VEGF), RunX2, OC, ALP were detected with quantitative RT-PCR; The protein expression of VEGF and RunX2 were detected with Western-blotting.

RESULTSIn CKO mice, the trabecular number, volume, thickness, bone density, mineral apposition rate (MAR), the expression of VEGF, RunX2, OC, ALP on mRNA level and the expression of VEGF, RunX2 on protein level decreased significantly compared with WT mice especially in 8 weeks after operation.

CONCLUSIONSThe bone formation ability of osteoblasts in CKO mice was reduced compared with WT mice after ovariotomy. HIF-1alpha can regulate the bone formation ability of osteoblasts in postmenopausal osteoporosis.

Animals ; Blotting, Western ; Core Binding Factor Alpha 1 Subunit ; genetics ; metabolism ; Disease Models, Animal ; Female ; Femur ; metabolism ; pathology ; physiopathology ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit ; genetics ; physiology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Osteoblasts ; metabolism ; physiology ; Osteoporosis, Postmenopausal ; genetics ; metabolism ; physiopathology ; Ovariectomy ; Random Allocation ; Reverse Transcriptase Polymerase Chain Reaction ; Vascular Endothelial Growth Factor A ; genetics ; metabolism

OBJECTIVETo evaluate the role of sclerostin in bone loss of postmenopausal Chinese women with type 2 diabetes mellitus.

METHODSThe postmenopausal patients suffering from type 2 diabetes mellitus and age, body mass index, and duration of menopause matched healthy controls were enrolled into this cross-sectional study according to criteria of inclusion and exclusion. The serum sclerostin level and bone mineral density of the anterior-posterior lumbar spine (L1-L4), femoral neck, and total hip were determined by using a quantitative sandwich ELISA kit and dual X-ray absorptiometry, respectively. Meanwhile, the clinical and laboratory indexes of bone mineral metabolism were analyzed. Associations between serum sclerostin level and bone mineral density as well as bone turnover markers were evaluated by linear regression analysis.

RESULTSFinally, 265 postmenopausal women with type 2 diabetes and 225 non-diabetic women were recruited in the diabetic group and control group, respectively. Serum sclerostin level of the diabetic group was significantly higher than that of the control group (48.2±19.4 vs. 37.2±18.6 pmol/L, P<0.001) and was increased with age in both groups (diabetic group, r=0.374, P<0.001; control group, r=0.312, P<0.001). In type 2 diabetes patients, serum sclerostin concentration was positively correlated with hemoglobin A1c level (r=0.237; P=0.021). Biochemical bone turnover markers, intact parathyroid hormone and bone-specific alkaline phosphatase, were negatively associated with serum sclerostin level (r=-0.138, P=0.078 and r=-0.265, P<0.001). Conversely, the positive correlation between sclerostin and C-terminal cross-linking telopeptide of type I collagen was found in diabetic patients (r=0.354, P<0.001). Serum sclerostin levels of the diabetic group were positively correlated with bone mineral density of the lumbar spine, femoral neck, and total hip (r=0.324, 0.367, and 0.416, respectively; all P<0.001).

CONCLUSIONSSclerostin might participate in the pathogenesis of bone loss of type 2 diabetes. The high sclerostin level might serve as a marker of increased osteocyte activity in postmenopausal patients with type 2 diabetes mellitus.

Aged ; Alkaline Phosphatase ; blood ; Asian Continental Ancestry Group ; Biomarkers ; blood ; Bone Morphogenetic Proteins ; blood ; China ; epidemiology ; Diabetes Mellitus, Type 2 ; blood ; epidemiology ; Female ; Genetic Markers ; Hemoglobin A ; metabolism ; Humans ; Middle Aged ; Osteocytes ; metabolism ; pathology ; Osteoporosis, Postmenopausal ; blood ; epidemiology ; Parathyroid Hormone ; blood ; Retrospective Studies