OBJECTIVETo study the effect and mechanism of chimonin on pulmonary arterioles I and III type collagen metabolism in pulmonary hypertension rats induced by chronic hypoxic hypercapnia.

METHODSThirty-six Sprague-Dawley rats were randomly divided into three groups: normal control group(A), hypoxic hypercapnic group(B), hypoxic hypercapnia + chimonin group(C). Collagen I, III and their mRNA, Blood CO concentration (COHb%), activity of HO-1 in blood serum and lung homogenate, content of hydroxyproline in lung homogenate, pulmonary arteriole micromorphometric index were observed.

RESULTSHypoxic hypercapnic rats's mPAP, Hyr of lung homogenate, content of I type collagen and I type collagen mRNA in pulmonary arterioles, were significantly higher than those in control group, pulmonary vessel remodeling of hypoxic hypercapnic rats was significant, those changes in hypercapnia + chimonin group were significantly lower than those in hypoxic hypercapnic group. Blood CO concentration, activity of HO-1 in blood serum and lung homogenate in rats of hypoxic hypercapnic rats were significantly higher than those of control group, and those of hypercapnia + chimonin group were even higher than hypoxic hypercapnic group (P < 0.01). There was no significant difference in mCAP, content of III type collagen and their mRNA in three groups (P > 0.05).

CONCLUSIONChimonin can reduce pulmonary hypertension and pulmonary vessel remodeling induced by hypoxic hypercapnia through inhibiting proliferation of collagen I, the mechanism maybe is up regulating endogenous carbon monoxide system.

Animals ; Arterioles ; metabolism ; Carbon Monoxide ; metabolism ; Chronic Disease ; Collagen Type I ; metabolism ; Collagen Type III ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Hypercapnia ; complications ; physiopathology ; Hypertension, Pulmonary ; etiology ; metabolism ; physiopathology ; Hypoxia ; complications ; physiopathology ; Lung ; blood supply ; Male ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo study the bone mineral density (BMD) of the third lumbar vertebrae and the Ward's triangle in the femoral neck and serum type I collagen C-telopeptide (CTx) level in female adults and provide scientific evidence for diagnosis and prevention of osteoporosis.

METHODSAccording to the inclusion criteria, 653 female adults were examined for BMD of the third lumbar vertebrae and the Ward's triangle in the femoral neck and the level of serum CTx.

RESULTSThe peak of BMD in the third lumbar vertebrae occurred in 30-39 years of age, and that of the Ward's triangle in the femoral neck occurred in 20-29 years of age, showing significant differences between the age groups (P<0.01). The BMD of the Ward's triangle in the femoral neck decreased earlier than that of the third lumbar vertebrae by one age period. The level of serum CTx increased with age, showing significant differences between the age groups (P<0.01) but not between the 20-29 years and the 30-39 groups, or between 30-39 and the 40-49 years groups. The prevalence of osteoporosis increased also with age, and osteoporosis in the third lumbar vertebrae increased rapidly in the 50-59 years and the 60-69 years groups, maintaining a high level in older ages. The prevalence of osteoporosis in the Ward's triangle in the femoral neck increased obviously after the peak of BMD, maintaining a significantly higher level than that of the third lumbar vertebrae in the same age group.

CONCLUSIONSThe BMD in the third lumbar vertebrae and the level of serum CTx undergo obvious changes with age, especially in menopause. There is no obvious relation between decreased BMD in the Ward's triangle in the femoral neck and menopause.

Adult ; Aged ; Bone Density ; China ; Collagen Type I ; blood ; Female ; Femur Neck ; metabolism ; Humans ; Lumbar Vertebrae ; metabolism ; Middle Aged ; Peptides ; blood ; Young Adult

PURPOSE: To examine the influence of ovariectomy (OVX) on bone turnover and trabecular bone mass at the 3 clinically important skeletal sites in mature cynomolgus monkeys. MATERIALS AND METHODS: Six female cynomolgus monkeys, aged 17-21 years, were randomized into 2 groups by the stratified weight: the OVX and sham-operation groups (n = 3 in each group). The experimental period was 16 months. Lumbar bone mineral density (BMD) in vivo and serum and urinary bone turnover markers were longitudinally measured, and peripheral quantitative computed tomographic and bone histomorphometric analyses were performed on trabecular bone of the lumbar vertebra, femoral neck, and distal radius at the end of the experiment. RESULTS: OVX induced in a reduction in lumbar BMD compared with the sham controls and the baseline, as a result of increased serum levels of bone-specific alkaline phosphatase and urinary levels of cross-lined N- and C-terminal telopeptides of type I collagen. Furthermore, OVX induced reductions in trabecular volumetric BMD and trabecular bone mass compared with the sham controls, with increased bone formation rate at the lumbar vertebra, femoral neck, and distal radius. CONCLUSION: The results indicated that OVX in mature cynomolgus monkeys (17-21 years of age) increased bone turnover and induced trabecular bone loss at the three skeletal sites compared with the sham controls. Thus, mature cynomolgus monkeys could be utilized for preclinical studies to examine the effects of interventions on bone turnover and trabecular bone mass at the 3 clinically important skeletal sites.
Alkaline Phosphatase/blood ; Animals ; *Bone Density ; Collagen Type I/urine ; Female ; Femur Neck/metabolism ; Lumbar Vertebrae/metabolism ; Macaca fascicularis/*physiology ; Ovariectomy/*adverse effects ; Radius/metabolism ; Random Allocation

OBJECTIVE: To determine the relation between serum concentration of retinol binding protein (RBP) 4 and markers of bone metabolism, bone mineral density (BMD) in patients with type 2 diabetes mellitus (T2DM). METHODS: A total of 82 patients newly diagnosed with T2DM and 46 subjects with normal glucose tolerance (NGT) enrolled in the cross-sectional study. Subset analyses were performed, dividing subjects on the basis of gender into M-T2DM, F-T2DM, M-NGT, and F-NGT. The serum concentrions of RBP4, osteocalcin (OC) and C-terminal telopeptide of collagen type I (CTX) were measured with ELISA. The BMD was measured by dual-energy X-ray absorptiometry (DXA) with a Hologic QDR4500A device. RESULTS: In both the T2DM groups, lnRBP4 showed a positive relationship with lnCTX (M-T2DM, r=0.564, P<0.01; F-T2DM, r=0.386, P=0.018), but no association with lnOC. After adjusting for age, smoking, creatinine clearance rate (CCr), and waist-to-hip ratio (WHR), lnRBP4 still showed a strong association with lnCTX in the M-T2DM group (r'=0.536, P<0.01), but not in F-T2DM (r'=0.317, P=0.072). In the NGT group, there was no relation between lnRBP4 and lnCTX or lnOC. LnRBP4 showed no association with BMD in all groups. CONCLUSION The level of serum RBP4 may be correlated with the bone metabolism in patients with T2DM.
Adult ; Aged ; Bone Density ; Bone and Bones ; metabolism ; Collagen Type I ; blood ; Cross-Sectional Studies ; Diabetes Mellitus, Type 2 ; blood ; metabolism ; Female ; Humans ; Male ; Middle Aged ; Osteocalcin ; blood ; Peptides ; blood ; Retinol-Binding Proteins, Plasma ; metabolism

OBJECTIVEThe aim of this study was to access the relationship of osteolytic bone metabolic markers such as serum type I collagen carboxy-terminal telopeptide (sICTP), N-terminal cross-linked telopeptides of type I collagen (uNTx), urinary pyridinoline (uPyd) with the therapeutic effect in breast cancer patients with bone metastases.

METHODS120 patients with breast cancer were included in this study. The levels of sICTP, uNTx and uPYD were measured by ELISA assay. The differences were compared between patients with and without bone metastasis. The patients with bone metastasis were treated and followed up as clinically indicated.

RESULTSThe levels of all above mentioned biomarkers in patients with bone metastasis were significantly higher than that in patients without bone metastasis (P < 0.01). A significant correlation was found between each two markers (r > 0.5, P < 0.01). The biomarkers were examined again in 45 patients with bone metastasis after treatment to evaluate the treatment response. The median follow-up was 10 months. Based on clinical evaluation criteria, 25 patients were responders and 20 were non-responders. For responders, after 3 months treatment, the levels of the three bone markers were significantly reduced (P = 0.025, P < 0.001, P < 0.001). But for non-responders, with progression of bone lesions, the levels of the three markers were significantly raised (P = 0.011, P = 0.002, P = 0.002). By means of multiple logistic regression with stepwise selection, the uPyd and uNTx activities were closely correlated with treatment response (OR = 17.0, P = 0.019; OR = 16.7, P = 0.015), however, the sICTP did not show any correlation with treatment response P = 0.841).

CONCLUSIONThe levels of sICTP, uNTx and uPyd may be used as indicators in assessment of the effect of antiresorptive treatment and evaluation of prognosis in breast cancer patient with bone metastases.

Adult ; Aged ; Amino Acids ; urine ; Biomarkers, Tumor ; metabolism ; Bone Neoplasms ; drug therapy ; metabolism ; secondary ; Breast Neoplasms ; drug therapy ; metabolism ; pathology ; Collagen ; urine ; Collagen Type I ; blood ; Disease Progression ; Female ; Follow-Up Studies ; Humans ; Middle Aged ; Peptides ; blood ; Remission Induction

OBJECTIVE: To determine the effect of curcumin on diabetic nephropathy in db/db mice and its possible mechanism. METHODS: Ten female db/db mice were randomly divided into 2 groups: one was treated with curcumin at 200 mg/(kg.d) and the other was a placebo group. Five age-matched db/m mice were grouped as the controls. In the curcumin group, curcumin was administered to db/db mice for 18 weeks. At the end of the experiment, the blood glucose and albumin were measured, and the kidney tissue sections were stained with PAS to observe the pathological changes. The expression of collagen IV and FN in the kidney was detected by immunohitochemistry staining. Western blot was used to detect the phosphorylation of signal transducer and activator of transcription 3 (STAT3) and IκB in the kidney. RESULTS: Compared with db/m mice, the weight and blood glucose of db/db mice were markedly increased, accompanied with heavy proteinuria, glomerulus hypertrophy, mesangial area expansion, thickening of basement membrane and ECM deposition. The phosphorylation of STAT3 was upregulated and the degradation of IκB was increased. Compared with the db/db mice, curcumin significantly decreased the urinary albumin, inhibited the phosphorylation of STAT3 and the degradation of IκB, and reduced the expression of collagen IV and FN in the kidney. CONCLUSION Curcumin can obviously decrease albuminuria and attenuate glomerular sclerosis in diabetic db/db mice by inhibiting phosphorylation of STAT3 and degradation of IκB.
Albuminuria ; Animals ; Blood Glucose ; Collagen Type IV ; metabolism ; Curcumin ; pharmacology ; Diabetes Mellitus, Type 2 ; Diabetic Nephropathies ; drug therapy ; Female ; Fibronectins ; metabolism ; I-kappa B Proteins ; metabolism ; Kidney ; drug effects ; metabolism ; Mice ; Phosphorylation ; Proteinuria ; STAT3 Transcription Factor ; metabolism

OBJECTIVETo investigate the effect of Qindan capsule (QC) on collagen synthesis and the mechanism underlying the process in spontaneously hypertensive rats (SHRs).

METHODSTwentyfour SHRs were divided into three groups: the hypertension model group, the QC treatment group, and the losartan treatment group. Eight Wistar Kyoto (WKY) rats were used as the normal control group. The systolic blood pressure (SBP) of the rats was monitored, and the thoracic aorta adventitia of the rats was segregated. The expressions of transforming growth factor 1 (TGF-β1), Smad3, and collagens I and were measured by histological staining and reverse transcription polymerase chain reaction.

RESULTSThe SBP was significantly higher in the model group than in the normal control group (P<0.01). However, a significant SBP-lowering effect was observed in QC or losartan treatment groups (P<0.05 or P<0.01) after 3 weeks of treatment. QC-treated rats showed a decrease of approximately 40 mm Hg, and the losartan-treated rats showed a decrease of approximately 50 mm Hg at the end of treatment compared with the beginning of treatment. The protein and gene levels of TGF-β1, Smad3, and collagens I and in the model group were significantly increased compared with those in the normal control group (P<0.01). However, the levels were significantly decreased in the QC or losartan treatment group compared with the model group (P<0.05 or P<0.01). However, there was no significant difference between the QC and losartan treatment groups (P<0.05).

CONCLUSIONSQC could exert its antihypertensive effect through down-regulating TGF-β1-stimulated collagen expressions. The TGF-β1/Smad3 signaling pathway may be involved in this process.

Adventitia ; drug effects ; metabolism ; pathology ; Animals ; Blood Pressure ; drug effects ; Blood Vessels ; drug effects ; metabolism ; pathology ; Capsules ; Collagen ; biosynthesis ; Collagen Type I ; genetics ; metabolism ; Collagen Type III ; genetics ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Losartan ; pharmacology ; Male ; RNA, Messenger ; genetics ; metabolism ; Rats ; Rats, Inbred SHR ; Rats, Inbred WKY ; Smad3 Protein ; genetics ; metabolism ; Staining and Labeling ; Systole ; drug effects ; Transforming Growth Factor beta1 ; genetics ; metabolism

OBJECTIVETo investigate the effect of platelet-rich fibrin (PRF) on human gingival fibroblasts (HGF) biological behavior such as proliferation, migration and collagen-I expression.

METHODSHuman healthy gingival tissues were cultured according to the explant technique to obtain primary cultures. PRF was prepared by means of Choukroun's. HGF were co-cultured with PRF membrane originating from the same donor as the explants, divided into three groups, PRF1 group, PRF2 group and blank control group. Methyl thiazolyl tetrazolium (MTT) assay was used for cytotoxicity and cell proliferation study, and enzyme-linked immunosorbent assay (ELISA) for collagen-I (COL-I) secretion study at the 1st, 3rd, 5th day respectively. Eluates from PRF membrane was prepared, and divided into three groups, PRF1 group, PRF2 group and blank control group. Transwell chamber was utilized to determine the effect of PRF membrane eluate on cell migration.

RESULTSThe A values of HGF in culture of the PRF1 (0.615 ± 0.036, 0.686 ± 0.006, 0.693 ± 0.004) and PRF2 groups (0.653 ± 0.023, 0.766 ± 0.034, 0.775 ± 0.053) were significantly higher than those of the control cultures (0.514 ± 0.020, 0.544 ± 0.006, 0.545 ± 0.009) (P < 0.01), but the difference between PRF1 and PRF2 group was not significant (P > 0.05). In each group at different time points, the HGF proliferation effect was significantly enhanced with time (P < 0.01). Cell migration test showed that the migration numbers of HGF in PRF1 and PRF2 groups (85.67 ± 2.94, 85.83 ± 1.47) were significantly higher than those of the control group (54.17 ± 2.48) (P < 0.01), but the difference between the two experimental groups was not significant (P > 0.05). COL-I secretion test exhibited that the A values of COL-I in PRF1 (0.184 ± 0.004, 0.200 ± 0.004, 0.204 ± 0.009) and PRF2 group (0.213 ± 0.008, 0.226 ± 0.005, 0.229 ± 0.006) were significantly higher than the A values of the control group (0.174 ± 0.002, 0.184 ± 0.002, 0.186 ± 0.003) (P < 0.01), but the difference between the two experimental groups was not significant (P > 0.05). In each group, the secretion level of COL-I increased significantly with time (P < 0.01).

CONCLUSIONSPRF could exert a positive effect on HGF biological behaviour and had clinical application potential in the treatment of gingival recession and in the periodontal tissue engineering when combined with seed cell HGF.

Adult ; Blood Platelets ; Cell Movement ; Cell Proliferation ; Collagen Type I ; metabolism ; Fibrin ; pharmacology ; Fibroblasts ; cytology ; secretion ; Gingiva ; cytology ; Humans ; Male ; Primary Cell Culture

BACKGROUNDSclerostin, expressed exclusively by osteocytes, is a negative regulator of bone formation. To gain insights into the action of sclerostin in postmenopausal osteoporosis, we evaluated serum sclerostin levels in postmenopausal women and investigated its possible associations with bone turnover markers in patients with postmenopausal osteoporosis.

METHODSWe detected serum sclerostin, and measured lumbar spine bone mineral density in 650 Chinese postmenopausal women. We also assessed serum levels of β-isomerized C-terminal crosslinking of type I collagen, intact N-terminal propeptide of type I collagen, N-mid fragment of osteocalcin, 25-hydroxyvitamin D, and estradiol.

RESULTSSerum sclerostin levels were lower in postmenopausal osteoporotic women compared with non-osteoporotic postmenopausal women ((38.79 ± 7.43) vs. (52.86 ± 6.69) pmol/L, P < 0.001). Serum sclerostin was positively correlated with lumbar spine bone mineral density (r = 0.391, P < 0.001) and weakly negatively correlated with β-isomerized C-terminal crosslinking of type I collagen, intact N-terminal propeptide of type I collagen, N-mid fragment of osteocalcin (r = -0.225, P < 0.001; r = -0.091, P = 0.046; r = -0.108, P = 0.018; respectively) in postmenopausal osteoporosis. There was no significant association of serum sclerostin with age, body mass index, 25-hydroxyvitamin D, and estradiol (r = -0.004, P = 0.926; r = 0.067, P = 0.143; r = 0.063, P = 0.165; r = -0.045, P = 0.324; respectively).

CONCLUSIONSclerostin may be involved in the pathogenesis of postmenopausal osteoporosis and may play a role in bone turnover.

Aged ; Bone Density ; Bone Morphogenetic Proteins ; blood ; Bone Remodeling ; Collagen Type I ; blood ; Female ; Genetic Markers ; Humans ; Lumbar Vertebrae ; Middle Aged ; Osteoporosis, Postmenopausal ; blood ; metabolism ; Peptide Fragments ; blood ; Peptides ; blood ; Procollagen ; blood

OBJECTIVES: To study the level of serum vitamin K₂ (VitK₂) and its association with bone metabolism markers osteocalcin (OC), type I procollagen amino-terminal peptide (PINP), and type I collagen carboxy-terminal peptide (CTX) in children. METHODS: A prospective analysis was performed on 1 732 children who underwent routine physical examination from October 2020 to October 2021. The serum levels of VitK₂ and 25-hydroxy vitamin D [25(OH)D] were measured. According to age, they were divided into four groups: <1 year, 1-3 years group, >3-6 years group, and >6-14 years. A total of 309 children with 25(OH)D≥50 nmol/L were screened out, and serum levels of OC, PINP, and CTX were measured to investigate the correlation of the serum levels of OC, PINP, and CTX with serum VitK₂ levels in different age groups. RESULTS: The prevalence rate of serum VitK₂ deficiency was 52.31% (906/1 732). The VitK₂ deficiency group had higher prevalence rates of overweight/obesity and growth pain (≥3 years of age) than the normal VitK₂ group (<i>Pi><0.05). There were differences in the prevalence rate of serum VitK₂ deficiency (<i>Pi><0.0083) and the serum level of VitK₂ (<i>Pi><0.05) between the 1-3 years group and the >6-14 years group. The <1 year group had a higher serum level of CTX and a lower serum level of PINP than the >3-6 years group and the >6-14 years group (<i>Pi><0.05). The <1 year group had a lower serum level of OC than the >6-14 years group (<i>Pi><0.05). Serum VitK₂ level was positively correlated with OC level (<i>r_si>=0.347, <i>Pi><0.01), and CTX level was negatively correlated with PINP level (<i>r_si>=-0.317, <i>Pi><0.01). CONCLUSIONS Serum VitK₂ deficiency may be associated with overweight/obesity. Serum VitK₂ may affect the level of OC and even bone health.
Child ; Humans ; Infant ; Biomarkers/metabolism* ; Collagen Type I/metabolism* ; Obesity/complications* ; Osteocalcin/metabolism* ; Overweight/complications* ; Peptide Fragments/metabolism* ; Peptides/metabolism* ; Procollagen/metabolism* ; Vitamin K/blood* ; Child, Preschool ; Adolescent ; Bone and Bones/metabolism*