BACKGROUND: Congenital scoliosis (CS) is a complex spinal malformation of unknown etiology with abnormal bone metabolism. Fibroblast growth factor 23 (FGF23), secreted by osteoblasts and osteocytes, can inhibit bone formation and mineralization. This research aims to investigate the relationship between CS and FGF23. METHODS: We collected peripheral blood from two pairs of identical twins for methylation sequencing of the target region. FGF23 mRNA levels in the peripheral blood of CS patients and age-matched controls were measured. Receiver operator characteristic (ROC) curve analyses were conducted to evaluate the specificity and sensitivity of FGF23. The expression levels of FGF23 and its downstream factors fibroblast growth factor receptor 3 (FGFr3)/tissue non-specific alkaline phosphatase (TNAP)/osteopontin (OPN) in primary osteoblasts from CS patients (CS-Ob) and controls (CT-Ob) were detected. In addition, the osteogenic abilities of FGF23-knockdown or FGF23-overexpressing Ob were examined. RESULTS: DNA methylation of the FGF23 gene in CS patients was decreased compared to that of their identical twins, accompanied by increased mRNA levels. CS patients had increased peripheral blood FGF23 mRNA levels and decreased computed tomography (CT) values compared with controls. The FGF23 mRNA levels were negatively correlated with the CT value of the spine, and ROCs of FGF23 mRNA levels showed high sensitivity and specificity for CS. Additionally, significantly increased levels of FGF23, FGFr3, OPN, impaired osteogenic mineralization and lower TNAP levels were observed in CS-Ob. Moreover, FGF23 overexpression in CT-Ob increased FGFr3 and OPN levels and decreased TNAP levels, while FGF23 knockdown induced downregulation of FGFr3 and OPN but upregulation of TNAP in CS-Ob. Mineralization of CS-Ob was rescued after FGF23 knockdown. CONCLUSIONS Our results suggested increased peripheral blood FGF23 levels, decreased bone mineral density in CS patients, and a good predictive ability of CS by peripheral blood FGF23 levels. FGF23 may contribute to osteopenia in CS patients through FGFr3/TNAP / OPN pathway.
Humans ; Osteopontin/genetics* ; Alkaline Phosphatase/metabolism* ; Receptor, Fibroblast Growth Factor, Type 3/metabolism* ; Scoliosis/genetics* ; Osteoblasts/metabolism* ; Calcinosis ; RNA, Messenger/metabolism* ; Bone Diseases, Metabolic/metabolism* ; Fibroblast Growth Factors/genetics*

OBJECTIVE: To explore the mechanism of the Notch1 signaling pathway in regulating osteogenic factors and influencing lumbar disc calcification. METHODS: Primary annulus fibroblasts from SD rats were isolated and subcultured in vitro. The calcification-inducing factors bone morphogenetic protein-2 (BMP-2) and basic fibroblast growth factor (b-FGF) were added to separate groups to induce calcification, which were referred to as the BMP-2 group and the b-FGF group, respectively. A control group was also set up, which was cultured in normal medium. Subsequently, cell morphology and fluorescence identification, alizarin red staining, ELISA, and quantitative real-time polymerase chain reaction (QRT-PCR) were performed to determine the effect of calcification induction. Cell grouping was performed again, including the control group, the calcification group (adding the inducer BMP-2), the calcification + LPS group(adding the inducer BMP-2 and the Notch1 pathway activator LPS), and the calcification + DAPT group (adding the inducer BMP-2 and the Notch1 pathway inhibitor DAPT). Alizarin red staining and flow cytometry were used to detect cell apoptosis, ELISA was used to detect the content of osteogenic factors, and Western blot was used to detect the expression of BMP-2, b-FGF, and Notch1 proteins. RESULTS: The induction factor screening results showed that the number of mineralized nodules in fibroannulus cells in BMP-2 group and b-FGF group was significantly increased, and the increase was greater in the BMP-2 group Meanwhile, ELISA and Western blot results showed that BMP-2, b-FGF and mRNA expression levels of BMP-2, b-FGF and Notch1 in the induced group were significantly increased (P<0.01). The results of the mechanism of Notch1 signaling pathway affecting lumbar disc calcification showed that compared to calcified group, the number of fibroannulus cell mineralization nodules, apoptosis rate, BMP-2, b-FGF content, the expression levels of BMP-2, b-FGF, and Notch1 proteins were further increased significantly However, the number of mineralization nodules, apoptosis rate, BMP-2 and b-FGF levels, BMP-2, b-FGF and Notch1 protein expression levels were decreased in the calcified +DAPT group (P<0.05 or P<0.01). CONCLUSION Notch1 signaling pathway promotes lumbar disc calcification through positive regulation of osteogenic factors.
Animals ; Rats ; Bone Morphogenetic Protein 2/metabolism* ; Calcinosis ; Cell Differentiation ; Cells, Cultured ; Lipopolysaccharides ; Osteogenesis ; Rats, Sprague-Dawley ; Receptor, Notch1/genetics* ; Signal Transduction

Metastatic calcinosis cutis refers to the deposition of calcium salts in normal tissue secondary to an underlying defect in calcium and/or phosphate metabolism. It commonly affects periarticular areas in patients with chronic renal failure. We report a case of a 51-year-old man with a past medical history of peritoneal dialysis for chronic renal failure, who presented with multiple yellowish nodules on his right thumb. In view of the asymptomatic non-inflamed fluctuating nodules, the differential diagnoses included bacterial, tuberculous, atypical mycobacterial, or fungal infections. Histopathological and radiological examinations revealed calcifications in the right thumb and shoulder with elevated serum phosphorus and parathyroid hormone levels. The lesions improved after the patient was switched from peritoneal dialysis to hemodialysis. We report a case of metastatic calcinosis cutis in a patient with chronic renal failure. We emphasize the importance of imaging for accurate diagnosis and follow-up of calcinosis cutis and that hemodialysis scores over peritoneal dialysis in the treatment of this condition.
Calcinosis ; Calcium ; Diagnosis ; Diagnosis, Differential ; Follow-Up Studies ; Humans ; Kidney Failure, Chronic ; Metabolism ; Middle Aged ; Parathyroid Hormone ; Peritoneal Dialysis ; Phosphorus ; Renal Dialysis ; Salts ; Shoulder ; Thumb

Adult ; Brain Diseases ; diagnostic imaging ; genetics ; Calcinosis ; diagnostic imaging ; genetics ; Calcium ; metabolism ; Humans ; Middle Aged ; Neurodegenerative Diseases ; diagnostic imaging ; genetics ; Retrospective Studies ; Tomography, X-Ray Computed

With the population aging and declining incidence of rheumatic heart disease, calcific aortic valve disease (CAVD) has become the most frequent valve disease and the common cause of aortic valve replacement. Patients with CAVD need to cope with a deteriorating quality of life and valve replacement is the only effective clinical option for the patients. Therefore, early pharmacotherapy is of great significance in prevention or slow-down of the progression of CAVD. For years CAVD was considered to be a passive wear and tear process of valves, but now it is recognized as an active and multi-factorial process. Histopathologic studies have revealed that inflammation, disorder of calcium and phosphorus metabolism and dyslipidemia are involved in the process of CAVD. Clinical trials of CAVD pharmacotherapy have been carried out based on those histopathologic studies. Statin, renin-angiotensin inhibitors and anti-osteoporosis drug are well studied in recent years. This article reviews the recent research progress of the pharmacotherapy for CAVD.
Angiotensin Receptor Antagonists ; therapeutic use ; Angiotensin-Converting Enzyme Inhibitors ; therapeutic use ; Aortic Valve ; pathology ; Aortic Valve Stenosis ; complications ; drug therapy ; etiology ; Calcinosis ; complications ; drug therapy ; etiology ; Calcium Metabolism Disorders ; complications ; Disease Progression ; Dyslipidemias ; complications ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; therapeutic use ; Inflammation ; complications ; Phosphorus Metabolism Disorders ; complications ; Quality of Life

Aortic valve calcification is a common disease in the elderly, but its cellular and molecular mechanisms are not clear. In order to verify the hypothesis that Wnt/β-catenin signaling pathway is involved in the process of calcification of aortic valve, porcine aortic valve interstitial cells (VICs) were isolated, cultured and stimulated with oxidized low density lipoprotein (ox-LDL) for 48 h to induce the differentiation of VICs into osteoblast-like cells. The key proteins and genes of Wnt/β-catenin signaling pathway, such as glycogen synthase kinase 3β (GSK-3β) and β-catenin, were detected by using Western blotting and real-time polymerase chain reaction (PCR). The results showed that the VICs managed to differentiate into osteoblast-like cells after the stimulation with ox-LDL and the levels of proteins and genes of GSK-3β and β-catenin were increased significantly in VICs after stimulation for 48 h (P<0.05). It is suggested that Wnt/β-catenin signaling pathway may play a key role in the differentiation of VICs into osteoblast-like cells and make great contribution to aortic valve calcification.
Alkaline Phosphatase ; genetics ; metabolism ; Animals ; Aortic Valve ; metabolism ; pathology ; Aortic Valve Stenosis ; Blotting, Western ; Bone Morphogenetic Protein 2 ; genetics ; metabolism ; Calcinosis ; Cell Differentiation ; drug effects ; genetics ; Cells, Cultured ; Gene Expression ; drug effects ; Glycogen Synthase Kinase 3 ; genetics ; metabolism ; Lipoproteins, LDL ; pharmacology ; Osteoblasts ; drug effects ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Swine ; Wnt Signaling Pathway ; genetics ; physiology ; beta Catenin ; genetics ; metabolism

The term tumoral calcinosis in used to describe the deposition of nodular calcareous masses in the soft tissue around large joints, such as the hips, shoulders, and elbows. Although the cause has not yet been clearly determined, according to the hypothesis, failure of phosphorus metabolism in the proximal tubule in kidney, chronic renal disease and hyperparathyroidism may cause tumoral calcinosis. No cases of tumoral calcinosis treated with surgical resection in chronic renal failure patients on hemodialysis, so called uremic tumoral calcinosis, have been reported in Korea. The authors experienced the case of a 57-year-old woman with chronic kidney disease on hemodialysis who presented with a mass around the hip. We made a diagnosis using plain radiographs, magnetic resonance imaging, and computed tomography of tumoral calcinosis, and treated the patient successfully with surgical resection. We report on a case of uremic tumoral calcinosis with a review of the literature.
Calcinosis* ; Diagnosis ; Elbow ; Female ; Hip ; Hip Joint* ; Humans ; Hyperparathyroidism ; Joints ; Kidney ; Kidney Failure, Chronic ; Korea ; Magnetic Resonance Imaging ; Metabolism ; Middle Aged ; Phosphorus ; Renal Dialysis* ; Renal Insufficiency, Chronic ; Shoulder

OBJECTIVETo investigate the association of fetuin-A with residual renal function and carotid artery calcification in patients with chronic kidney disease (CKD).

METHODSBlood examples were collected form 60 CKD patients in stages CKD3 to CKD5 (20 patients per stage) for measurement of serum fetuin-A, albumin, calcium, phosphorus and parathyroid hormone, cholesterol, triglycercide, low-density lipoprotein, and high-density lipoprotein. MDRD equation was used to calculate the estimated glomerular filtration rate (eGFR), and ELISA was used to detect serum fetuin-A. Color Doppler ultrasound was performed to measure carotid intima-media thickness (CIMT).

RESULTSAs the eGFR decreased, serum fetuin-A significantly decreased in CKD5 stage compared with that in CKD4 stage (P<0.05); compared with that in CKD3 stage, serum fetuin-A level was significantly lowered in CKD4 stage (P<0.05). Linear regression analysis suggested a significant positive correlation between fetuin-A and eGFR. The rate of carotid artery calcification was the highest in CKD5 stage. Rank correlation analysis showed a negative correlation between fetuin-A and cIMT, and logistic regression analysis identified decreased serum Fetuin-A as a risk factor of carotid artery calcification.

CONCLUSIONSerum fetuin-A decreases following the decrease in eGFR, and decreased serum Fetuin-A level is a risk factor of carotid artery calcification in CKD patients.

Adult ; Calcinosis ; etiology ; Carotid Artery Diseases ; etiology ; Carotid Intima-Media Thickness ; Female ; Glomerular Filtration Rate ; Humans ; Male ; Middle Aged ; Renal Insufficiency, Chronic ; blood ; complications ; physiopathology ; Risk Factors ; alpha-2-HS-Glycoprotein ; metabolism

OBJECTIVETo investigate the morphological features, immunohistochemical phenotype, diagnosis and differential diagnosis of collagenous spherulosis of the breast.

METHODSClinicopathologic observation, immunohistochemistry using EnVision method and histochemical staining were applied in 33 cases of collagenous spherulosis of the breast.

RESULTSCollagenous spherulosis of the breast was a benign lesion, consisting of proliferative myoepithelial and ductal epithelial cells. These cells were arranged in a cribriform pattern with esinophilic, round, oval or star-shaped fibrillary spherules in the lumen.SMA, calponin and p63 by immunohistochemistry identified the proliferative myoepithelium, while E-cadherin identified the proliferative ductal epithelial cells. The esinophilic spherules were stained with collagen type IV, AB-PAS and reticulin. Collagenous spherulosis was often found in sclerosing adenosis.

CONCLUSIONSCollagenous spherulosis of the breast is often associated with other diseases. It has special morphological presentation and is easily confused with malignant tumors such as adenoid cystic carcinoma or cribriform carcinoma in situ, and needs to be differentiated from these disease entities.

Actins ; metabolism ; Adult ; Aged ; Breast ; pathology ; Breast Diseases ; metabolism ; pathology ; Cadherins ; metabolism ; Calcinosis ; Calcium-Binding Proteins ; metabolism ; Collagen ; metabolism ; Collagen Type IV ; metabolism ; Female ; Humans ; Hyperplasia ; Membrane Proteins ; metabolism ; Microfilament Proteins ; metabolism ; Middle Aged

This study aimed to determine and quantitate the mammographic and sonographic characteristics in 13 cases of solid neuroendocrine breast carcinoma (NEBC) and to analyze the association of radiological findings with the clinical and histopathologic findings. The clinical data and imaging findings of 13 female patients with histologically confirmed solid NEBC were reviewed. Imaging data were evaluated by two radiologists for a consensual diagnosis. All patients presented with one palpable mass; only 1 experienced occasional breast pain, and 5 complained of fluid discharge. In 7 patients, the masses were firm and mobile. Regional lymph node metastasis was noted in only 1 patient. For the 10 patients who underwent mammography, 6 had a mass, 1 had clustered small nodules with clustered punctuate microcalcifications, 2 had asymmetric focal density, and 1 had solitary punctuate calcification. Most of the masses had irregular shape with indistinct or microlobulated margins. For the 9 patients who underwent ultrasonography (US), 9 masses were depicted, all of which were hypoechoic, mostly with irregular shape and without acoustic phenomena. Different types of acoustic phenomena were also identified. One patient had developed distant metastases during follow-up. NEBC has a variety of presentations, but it is mostly observed on mammograms as a dense, irregular mass with indistinct or microlobulated margins. Sonographically, it typically presents as an irregular, heterogeneously hypoechoic mass with normal sound transmission. Histories of nipple discharge and calcification observed using imaging are not rare.
Adult ; Aged ; Biopsy, Fine-Needle ; Breast Neoplasms ; diagnostic imaging ; metabolism ; pathology ; Calcinosis ; diagnostic imaging ; Carcinoma, Neuroendocrine ; diagnostic imaging ; metabolism ; pathology ; Chromogranin A ; metabolism ; Female ; Follow-Up Studies ; Humans ; Ki-67 Antigen ; metabolism ; Lymphatic Metastasis ; Mammography ; Middle Aged ; Phosphopyruvate Hydratase ; metabolism ; Receptors, Estrogen ; metabolism ; Receptors, Progesterone ; metabolism ; Synaptophysin ; metabolism ; Ultrasonography, Mammary