Serum Bone Morphogenetic Protein-7 Research Articles

Expression of sclerostin and bone morphogenetic protein-7 (BMP-7) in serum of patients with chronic kidney disease-mineral and bone disorder (CKD-MBD) and their correlation with calcium and phosphorus metabolism

Calcium and phosphorus metabolism involves in patients with chronic kidney disease-mineral and bone disorder (CKD-MBD). Sclerostin and bone morphogenetic protein-7 (BMP-7) are closely related to bone formation. This study aims to assess sclerostin and BMP-7’s role in renal function, blood calcium and phosphorus in CKD-MBD. 86 CKD-MBD patients were collected as the case group and 86 healthy subjects were selected as control group. ELISA was used to detect Sclerostin and BMP-7 serum level. The automatic biochemical analyzer was used to detect liver and kidney function. Blood calcium and phosphorus level, and iPHT level was detected by immunoradiation. No differences were found regarding age, gender, and BMI between case group and control group (P > 0.05). Compared to controls, CKD-MBD patients had significantly reduced blood calcium and eGFR level, and increased Scr, BUN, blood phosphorus and iPTH level (P < 0.05) with increased Sclerostin (t = 33.86, P < 0.001), and reduced BMP-7 level (t = 329.38, P < 0.001). Scr, BUN, blood phosphorus levels and iPTH were correlated with Sclerostin positively (P < 0.05) and BMP-7 negatively (P < 0.05). eGFR and blood calcium were correlated with Sclerostin negatively (P < 0.05) and BMP-7 positively (P < 0.05). Scr, eGFR, blood calcium levels, blood phosphorus levels, and iPTH are independent risk factors for serum Sclerostin and BMP-7 level. Sclerostin and BMP-7 changes may be important factors affecting the occurrence of CKD-MBD. Renal function, blood calcium and blood phosphorus are independent risk factors for serum Sclerostin and BMP-7 level.

Serum level of bone morphogenetic protein-7 in relation to entheseal ultrasonography in ankylosing spondylitis patients

Aim of the workTo assess serum level of bone morphogenetic protein-7 (BMP-7) and to study its relation to clinical and sonographic assessment of peripheral enthesitis in ankylosing spondylitis (AS) patients. Patients and methodsThis study involved 49 AS patients and 40 matched controls. The serum BMP-7 level was determined by enzyme linked immunosorbant assay (ELISA). Entheses were assessed by musculoskeletal ultrasound (MSUS) and scored using Madrid Sonographic Enthesitis Index (MASEI). The AS disease activity score-C-reactive protein (ASDAS-CRP), Bath AS disease activity index (BASDAI) and Bath AS Functional Index (BASFI) were assessed. ResultsPatients were 45 males and 4 females with a mean age of 35.57 ± 9.71 years and median disease duration of 10 (2–28) years. US lesions were frequently found at the insertions of Achilles (76.5%), quadriceps (57.1%), plantar fascia (51%) and triceps (43.8%) tendons. Serum level of BMP-7 was significantly increased in patients (41.8 ng/ml) compared to controls (38.5 ng/ml) (p = 0.031). BMP-7 serum level significantly correlated with age (p = 0.03), disease duration (p < 0.001) and BASFI (p = 0.02) but did not correlate with ASDAS CRP, BASDAI, clinical enthesitis or total MASEI. Total MASEI correlated significantly with age, disease duration, ASDAS-CRP, BASDAI and BASFI. MASEI is a good predictor of activity in AS patients at a cut-off score of 9. ConclusionAS patients have a significant higher level of serum BMP-7 compared to control which indicates that it may play an important pathogenetic role in AS. However, this level did not correlate with either clinical or sonographic assessment of peripheral enthesitis.

Effects of ergosteroside combined risedronate on fracture healing and BMP-2, BMP-7 and VEGF expression in rats.

ABSTRACTPurposeTo evaluate the effect of ergosterol combined with risedronate on fracture healing.MethodsSixty male Sprague Dawley fracture model rats were assigned into group A (n=20), group B (n=20), and group C (n=20) at random. All rats were fed by gavage until their sacrifice as it follows: group A with ergosteroside and risedronate, group B with risedronate, and group C with saline solution. At weeks 2 and 4, 10 rats of each group were sacrificed. Healing effect and bone tissue changes in the fractures site were assessed by using hematoxylin and eosin stain histology. Enzyme-linked immunosorbent assay was used to detect the expression of serum bone morphogenetic protein-2 (BMP-2), bone morphogenetic protein-7 (BMP-7), and vascular endothelial growth factor (VEGF). Reverse transcriptase polymerase chain reaction was applied to detect the expression of osteoprotegerin (OPG) mRNA, osteocalcin (OCN) mRNA and core-binding factor subunit-?1 (CBF-?1) mRNA.ResultsIn terms of serum BMP-2, BMP-7, and VEGF expression at weeks 2 and 4 after gavage, group A < group B < group C (P<0.05). At week 4 after gavage, serum VEGF expression in the three groups harbored positive relationship with serum BMP-2 and BMP-7 expression (P<0.05). Regarding serum OPG, OCN and CBF-?1 mRNA expression at weeks 2 and 4 after gavage, group A <group B <group C (P<0.05). Hematoxylin and eosin staining results showed that the recovery effect of trabecular bone and callus in the cases of group A was better than the other two groups after intragastric administration.ConclusionErgosteroside combined risedronate can patently ameliorate the healing effect of fracture in rats.

Changes in bone formation regulator biomarkers in early axial spondyloarthritis.

The hallmark of advanced axial SpA (axSpA) is spine ankylosis due to excessive ectopic bone formation. This prospective study aimed to describe the changes in serum levels of different regulators [sclerostin, dickkopf-1 (DKK-1)] and markers of bone formation [bone morphogenetic protein 7 (BMP-7)] over 5 years in early axSpA patients and to assess determinants of such changes. The DEvenir des Spondyloarthropathies Indifférenciées Récentes cohort is a prospective, multicentre French study of 708 patients with early (>3 months-<3 years) inflammatory back pain suggestive of axSpA. Serum levels of BMP-7, sclerostin and DKK-1 were assessed at baseline and after 2 and 5 years. Changes in bone formation regulators over time were analysed using mixed linear models. Serum BMP-7 significantly increased over time, with a median relative change of 223.7% [interquartile range (IQR) 0-10700 (0.17 pg/ml/month), P < 0.001]. Serum sclerostin significantly increased over time, with a median relative change of 14.8% [IQR -7.9-41.4% (0.001 ng/ml/month), P < 0.001]. Serum DKK-1 did not significantly change over time. Serum BMP-7 increased over time in active disease (Ankylosing Spondylitis Disease Activity Score with CRP ≥1.3, P = 0.01), but the increase was less pronounced with TNF inhibitor (TNFi) use (P < 0.001). No determinant was associated with serum sclerostin change. Serum BMP-7 change over 5 years was related with inflammation; it was increased in active disease, but the increase was low with TNFi use. Serum sclerostin levels significantly increased over time, but to a lesser degree than for serum BMP-7. https://clinicaltrials.gov/, NCT01648907.

Noninvasive method of differentiating diabetic nephropathy and nondiabetic renal disease using serum bone morphogenetic protein-7 and transforming growth factor-beta 1 levels in patients with type-2 diabetes mellitus.

Diabetic nephropathy (DN), one of the major complications of diabetes mellitus, is diagnosed by the presence of pedal edema, 24-h proteinuria >300 mg/day, and retinopathy. However, in view of variable clinical presentations and deviation from the above-said clinical features, it has become difficult to diagnose DN or the presence of nondiabetic renal disease (NDRD). Many biomarkers have been identified which could predict the progression of DN. Despite such advancement in science, it is still difficult to differentiate between DN and NDRD. Diabetes is a state of chronic inflammation. Among the pro-inflammatory cytokines, it has been shown that transforming growth factor-beta (TGF-β) and bone morphogenetic protein-7 (BMP-7) play a key role in the development and progression of DN. We assessed whether the levels of serum BMP-7 and TGF-β can help differentiate between DN and NDRD, thus serving as surrogate markers of DN.

Effect of alprostadil on serum bone morphogenetic protein 7 and transforming growth factor-β1 in patients with diabetic nephropathy

Objective To investigate the clinical efficacy of alprostadil in the treatment of diabetic nephropathy, and its effect on serum bone morphogenetic protein 7(BMP-7)and transforming growth factor-β1(TGF-β1)levels in patients. Methods From January 2014 to January 2016, 120 cases of diabetic nephropathy in the People's Hospital of Beilun District were selected in the study.According to different treatment methods, the patients were divided into study group and control group, with 60 cases in each group.The two groups were treated with basic treatment, the study group was treated with alprostadil for 8 weeks.The clinical efficacy and serum levels of BMP-7 and TGF-β1 were compared between the two groups. Results There were no significant differences in serum BMP-7 and TGF-β1 between the two groups before treatment(P>0.05). After treatment, the serum BMP-7[(17.54±3.90)pg/mL]in the study group was higher than that in the control group[(15.20±2.96)pg/mL](t=3.607, P 0.05). After treatment, the levels of UAER, Hcy, Scr, BUN in the study group were(89.62±17.74)g/min, (23.55±4.17)mol/L, (64.2±8.5)mol/L, (6.70±0.96)mmol/L, which were significantly lower than those in the control group[(118.50±21.18)g/min, (29.69±4.82)mol/L, (74.7±9)mol/L, (7.52±0.89)mmol/L](t=8.097, 7.462, 6.57, 4.852, all P<0.05). Conclusion Alprostadil has better clinical effect on diabetic nephropathy, and can significantly improve serum BMP-7 and TGF-β1 levels. Key words: Diabetic nephropathy; Bone morphogenetic protein-7; Transforming growth factor beta 1; Alprostadil

Decreased BMP-7 and p-Smad1/5/8 expression, and increased levels of gremlin in hepatocellular carcinoma.

The aim of the present study was to investigate the expression of bone morphogenetic protein-7 (BMP-7), gremlin, and p-Smad/1/5/8 in carcinomatous and para-carcinoma tissue specimens from patients with hepatocellular carcinoma (HCC). The association of serum BMP-7 levels with clinicopathological parameters was examined to assess its relevance as a clinical biomarker for HCC. A total of 27 patients with HCC and 7 healthy subjects were included. Gene expression levels of BMP-7 and p-Smad1/5/8 were examined by reverse transcription-quantitative polymerase chain reaction. Immunohistochemical and western blot analysis were performed to determine the protein expression of target genes. The serum levels of BMP-7 were assessed by enzyme linked immunosorbent assay. The mRNA and protein expression of BMP-7 and gremlin were significantly down- and upregulated in HCC tumor tissues, respectively, compared with para-carcinoma tissues (P<0.05). The association of BMP-7 and gremlin expression with the differentiation status of HCC was also analyzed. There was a relatively higher level of BMP-7 and a lower level of gremlin expression in tumor tissues from patients with highly differentiated HCC when compared with poorly or moderately differentiated HCC (BMP-7, F=42.29, P<0.01; gremlin, F=37.93, P<0.01). Furthermore, the level of BMP-7 and p-Smad1/5/8 was decreased in patients with advanced stages of HCC, when compared with stage I HCC. The findings from the present study suggest that the BMP-7/p-Smad signaling pathway may be involved in the pathogenesis of HCC. The serum levels of BMP-7 may serve as a potential biomarker for HCC.

Are bone morphogenetic protein-7 (BMP-7) serum levels correlated with development of hepatic fibrosis?

Bone morphogenetic protein-7 (BMP-7) is a key protein in organogenesis and liver development. The protein has been studied in the context of liver fibrosis and regeneration. The aim of the present study was to explore any possible association between fibrosis levels (as revealed by liver biopsy) and serum BMP-7 levels. A total of 189 patients with chronic hepatitis B and 51 healthy controls were enrolled in the study. The study group contained 120 (63.5%) males and 69 (36.5%) females, and the control group contained 25 males (49.0%) and 26 females (51%). In general, serum BMP-7 values of patients were higher than those of controls (p = 0.001). Serum BMP-7 values of patients with liver fibrosis of stages 1, 2, 3, or 4 were higher than control values (all p values = 0.01), but the serum BMP-7 levels of patients with stage 5 fibrosis were similar to that of controls. Associations between fibrosis stage and the serum levels of BMP-7, ALT, HBVDNA, platelets, and albumin were all statistically significant (p = 0.001). The AUROC for the BMP-7 level in advanced stage fibrosis was found to be 0.23. The data were analyzed using the binary logistic regression analysis (backward stepwise method) and BMP-7, HBVDNA, and platelet levels were found to be risk factors associated with fibrosis (p values 0.031, 0.040, and 0.001, respectively). BMP-7 may play anti-inflammatory and anti-fibrogenic roles in the pathogenesis of chronic hepatitis B infection.

Bone Morphogenetic Protein-7 and disease progression in renal amyloidosis patients

Introduction: Chronic kidney disease (CKD) is an important health care problem with increasing incidence. Early diagnosis, recognition and interventions to avoid the disease progression have great value. Even some risk factors for disease progression have been described; there are still some dark spots. Transforming growth factors (TGFs), particularly bone morphogenetic protein-7 (BMP7) take place in renal fibrosis. Our study aimed to evaluate the association between serum BMP7 levels and the progression of CKD. Materials and methods: Our study has been conducted between January 2008 and December 2010. Decrease in GFR by 10%, doubling of serum creatinine and need for renal replacement therapy have been set as progression end-points. Totally 93 patients (48 female, 45 male) have been included. Baseline and end of follow-up BMP7 levels have been measured. Results: At the end of the follow-up, 46 of 93 patients have been considered as having progressive CKD. Higher levels of serum BMP7 levels have been found to be associated in progressive kidney disease. Discussion: Our results showed that BMP7 levels were higher in patients with progressive CKD, and also BMP7 to be associated with CKD progression. But this relationship was not statistically significant. In patients with progressive CKD, higher levels of proteinuria and blood pressure have been previously described. The effect of BMP7 on kidneys is not still clear, it is hypothesized that TGF-beta1 inhibition may alter renal fibrosis.

The relation between serum bone morphogenetic protein-7 and severity of enthesitis in psoriatic arthritis

The relation between serum bone morphogenetic protein-7 and severity of enthesitis in psoriatic arthritis

Oral Administration of Recombinant Adeno-associated Virus-mediated Bone Morphogenetic Protein-7 Suppresses CCl4-induced Hepatic Fibrosis in Mice

Fibrogenesis and hepatocyte degeneration are the main pathological processes in chronic liver diseases. Transforming growth factor-β1 (TGF-β1) is the key profibrotic cytokine in hepatic fibrosis. Bone morphogenetic protein-7 (BMP-7) is a potent antagonist of TGF-β1 and an antifibrotic factor. In this study, we generated a recombinant adeno-associated virus carrying BMP-7 (AAV-BMP-7) and tested its ability to suppress carbon tetrachloride (CCl(4))-induced hepatic fibrosis when orally administered to mice. Our results show that the ectopic expression of BMP-7 in gastrointestinal (GI) mucosa due to the AAV-BMP-7 administration led to the long-term elevation of serum BMP-7 concentrations and resulted in the drastic amelioration of CCl(4)-induced hepatic fibrosis in BALB/c mice. Immunostaining for α-smooth muscle actin (α-SMA) and desmin demonstrated that AAV-BMP-7 inhibited the activation of hepatic stellate cells (HSCs) in the fibrotic mouse liver. Moreover, the ectopic expression of BMP-7 promoted hepatocyte proliferation, as confirmed by an increase in the amount of proliferating cell nuclear antigen (PCNA)-positive hepatocytes in the mice that received AAV-BMP-7. Our results clearly indicate that BMP-7 is capable of inhibiting hepatic fibrosis and promoting hepatocyte regeneration. We suggest that oral AAV-BMP-7 could be developed into a safe, simple, and effective therapy for hepatic fibrosis.

Patients with polycystic ovarian syndrome (PCOS) have decreased serum levels of theca cell derived bone morphogenetic protein-7 (BMP-7): a new hormonal marker?

Polycystic ovary syndrome (PCOS) is a complex endocrine disorder with a vague definition. There are currently no hormonal markers specific to PCOS other than androgens for which the main sites of production are theca cells and ovarian stroma. Bone morphogenetic protein-7 (BMP-7) is a member of TGF–β superfamily exclusively expressed by theca and stromal cells. Therefore we aimed to determine the serum levels of BMP-7 in PCOS patients in comparison with controls. A controlled cross sectional study. 37 PCOS patients and 21 healthy controls were enrolled in the study. PCOS was defined by two of the following three features: 1) oligo/anovulation, 2) clinical and/or biochemical signs of hyperandrogenism, 3) polycystic ovaries on ultrasound. Blood samples were obtained in the early follicular phase except in 16 amenorrheic patients. BMP-7, AMH and free testosterone (fT) were measured by ELISA. FSH and LH were assayed with DPC method. Serum BMP-7 was significantly decreased in PCOS patients compared to control subjects (38.7 ± 4.3 vs. 74.7 ± 20.9 pg/mL, P<0.05) Controls were older than PCOS patients but BMI, FSH and fT levels were comparable. AMH, LH, and antral follicle counts (AFC) were significantly higher in PCOS patients than in controls. BMP-7 did not correlate with any of these variables in both groups.Tabled 1Control (Mean ± SD)PCO (Mean ± SD)PAge33.2 ± 5.727.4 ± 5.6<0.05BMI22.6 ± 3.924.1 ± 5.9NSFSH (mIU/mL)6.5 ± 2.35.7 ± 1.9NSLH (mIU/mL)6.5 ± 2.910.7 ± 7.1<0.05AMH (ng/mL)1.2 ± 1.53.8 ± 3.3<0.001Free testosterone (pg/mL)0.45 ± 0.30.6 ± 0.3NSAntral follicle count5.9 ± 4.113.5 ± 3.1<0.0001BMP-7 (pg/mL)74.7 ± 20.938.7 ± 4.3<0.05BMP-7: Bone morphogenetic protein-7 Open table in a new tab BMP-7: Bone morphogenetic protein-7 These results suggest that BMP-7 could be a new diagnostic hormonal marker for PCOS and may provide new insights into the pathogenesis of the disease.

Elevated Serum Bone Morphogenetic Protein 7 Levels and Clinical Outcome in Children with Biliary Atresia

Biliary atresia (BA) is one of the most serious liver disorders in children. The purposes of the present study were to investigate serum levels of bone morphogenetic protein 7 (BMP7) in BA children compared with healthy controls and to evaluate the association between serum BMP7 and the clinical outcome of BA patients post Kasai operation. Sixty-two BA patients post Kasai operation and 14 healthy controls were enrolled. The patients were divided into two groups according to their serum total bilirubin levels (TB<2, no jaundice vs. TB> or =2 mg/dL, persistent jaundice) and alanine aminotransferase levels (ALT<45, normal ALT vs. ALT> or =45 IU/L, elevated ALT). Serum BMP7 levels were determined by commercial enzyme-linked immunoabsorbent assay. The mean serum BMP7 was higher in BA patients compared with that of healthy controls (35.4+/-3.6 vs. 20.6+/-2.7 pg/mL, p=0.002). The BA patients with persistent jaundice had more elevated serum BMP7 levels than those without jaundice (59.5+/-6.5 vs. 20.3+/-1.6 pg/mL, p=0.001). There was also a correlation between serum total bilirubin and serum BMP7 levels (r=0.57, p<0.001). Moreover, the levels of serum BMP7 in BA patients with elevated ALT were significantly higher than those with normal ALT (41.6+/-4.7 vs. 22.4+/-4.2 pg/mL, p=0.003). Additionally, BA patients with portal hypertension had higher increased serum BMP7 levels compared to those without portal hypertension (45.3+/-4.9 vs. 18.7+/-2.8 pg/mL, p<0.001). The significant increment of serum BMP7 was associated with a deterioration of hepatic function and the progression of liver fibrosis. Serum BMP7 could be used as a prognostic marker to reflect disease severity and monitor disease progression in BA patients post Kasai operation.