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1.
Bone ; 60: 162-71, 2014 Mar.
Article in English | MEDLINE | ID: mdl-24333131

ABSTRACT

Myostatin is a member of the bone morphogenetic protein/transforming growth factor-ß (BMP/TGFß) super-family of secreted differentiation factors. Myostatin is a negative regulator of muscle mass as shown by increased muscle mass in myostatin deficient mice. Interestingly, these mice also exhibit increased bone mass suggesting that myostatin may also play a role in regulating bone mass. To investigate the role of myostatin in bone, young adult mice were administered with either a myostatin neutralizing antibody (Mstn-mAb), a soluble myostatin decoy receptor (ActRIIB-Fc) or vehicle. While both myostatin inhibitors increased muscle mass, only ActRIIB-Fc increased bone mass. Bone volume fraction (BV/TV), as determined by microCT, was increased by 132% and 27% in the distal femur and lumbar vertebrae, respectively. Histological evaluation demonstrated that increased BV/TV in both locations was attributed to increased trabecular thickness, trabecular number and bone formation rate. Increased BV/TV resulted in enhanced vertebral maximum compressive force compared to untreated animals. The fact that ActRIIB-Fc, but not Mstn-mAb, increased bone volume suggested that this soluble decoy receptor may be binding a ligand other than myostatin, that plays a role in regulating bone mass. This was confirmed by the significant increase in BV/TV in myostatin deficient mice treated with ActRIIB-Fc. Of the other known ActRIIB-Fc ligands, BMP3 has been identified as a negative regulator of bone mass. However, BMP3 deficient mice treated with ActRIIB-Fc showed similar increases in BV/TV as wild type (WT) littermates treated with ActRIIB-Fc. This result suggests that BMP3 neutralization is not the mechanism responsible for increased bone mass. The results of this study demonstrate that ActRIIB-Fc increases both muscle and bone mass in mice. Therefore, a therapeutic that has this dual activity represents a potential approach for the treatment of frailty.


Subject(s)
Activin Receptors/metabolism , Myostatin/metabolism , Osteogenesis , Anabolic Agents/pharmacology , Animals , Antibodies, Monoclonal/metabolism , Body Weight/drug effects , Bone Morphogenetic Protein 3/metabolism , Bone and Bones/diagnostic imaging , Bone and Bones/drug effects , Female , Mice , Mice, Inbred C57BL , Muscles/anatomy & histology , Muscles/drug effects , Organ Size/drug effects , Osteogenesis/drug effects , Parathyroid Hormone/pharmacology , Receptors, Fc/metabolism , X-Ray Microtomography
2.
J Dent Res ; 86(10): 951-5, 2007 Oct.
Article in English | MEDLINE | ID: mdl-17890670

ABSTRACT

The molecular mechanisms that maintain the equilibrium of odontoblast progenitor cells in dental pulp are unknown. Here we tested whether homeostasis in dental pulp is modulated by Twist-1, a nuclear protein that partners with Runx2 during osteoblast differentiation. Our analysis of Twist-1(+/-) mice revealed phenotypic changes that involved an earlier onset of dentin matrix formation, increased alkaline phosphatase activity, and pulp stones within the pulp. RT-PCR analyses revealed Twist-1 expression in several adult organs, including pulp. Decreased levels of Twist-1 led to higher levels of type I collagen and Dspp gene expression in perivascular cells associated with the pulp stones. In mice heterozygous for both Twist-1 and Runx2 inactivation, the phenotype of pulp stones appeared completely rescued. These findings suggest that Twist-1 plays a key role in restraining odontoblast differentiation, thus maintaining homeostasis in dental pulp. Furthermore, Twist-1 functions in dental pulp are dependent on its interaction with Runx2.


Subject(s)
Core Binding Factor Alpha 1 Subunit/physiology , Dental Pulp/cytology , Nuclear Proteins/physiology , Twist-Related Protein 1/physiology , Animals , Cell Differentiation/physiology , Cells, Cultured , Collagen Type I/biosynthesis , Core Binding Factor Alpha 1 Subunit/antagonists & inhibitors , Dental Pulp Calcification/physiopathology , Extracellular Matrix Proteins , Homeostasis/physiology , Mice , Mice, Mutant Strains , Odontoblasts/cytology , Odontoblasts/metabolism , Phosphoproteins , Protein Precursors/biosynthesis , Reverse Transcriptase Polymerase Chain Reaction , Sialoglycoproteins
3.
Med Sci Monit ; 7 Suppl 1: 292-3, 2001 May.
Article in English | MEDLINE | ID: mdl-12211739

ABSTRACT

A 69-year-old woman was admitted to our Department with the diagnosis of liver cyst. She had previously undergone liver cyst fenestration 10 years before. After abdominal spiral CT, the patient was qualified for laparotomy. A cystic formation was localized in the central part of the liver, in the 4th segment and was found to compress the hilar bile ducts. A 4.5 bisegmentectomy was performed. During the postoperative course, a biliary fistula was observed, which resolved spontaneously. The treatment was also complicated by myocardial infarction. The patient was discharged in good condition 30 days postoperatively. The pathological diagnosis revealed cystadenocarcinoma.


Subject(s)
Cystadenocarcinoma/diagnosis , Liver Neoplasms/diagnosis , Aged , Cystadenocarcinoma/pathology , Cystadenocarcinoma/surgery , Female , Humans , Liver Neoplasms/pathology , Liver Neoplasms/surgery , Time Factors
4.
Dev Biol ; 218(2): 354-66, 2000 Feb 15.
Article in English | MEDLINE | ID: mdl-10656775

ABSTRACT

We describe a novel transgene insertional mouse mutant with skeletal abnormalities characterized by a kinked tail and severe curvature of the spine. The disrupted locus is designated kkt for "kyphoscoliosis kinked tail." Malformed vertebrae including bilateral ossification centers and premature fusion of the vertebral body to the pedicles are observed along the vertebral column, and the lower thoracic and lumbar vertebrae are the most affected. Some of the homozygous kkt neonates displayed two backward-pointing transverse processes in the sixth lumbar vertebra (L6) that resembled the first sacral vertebra, and some displayed one forward- and one backward-pointing transverse process in L6. The fourth and fifth sternebrae were also fused, and the acromion process of the scapula was missing in kkt mice. The skeletal abnormalities are similar to those observed in the mouse mutant undulated (un). The transgene is integrated at the distal end of chromosome 2 close to the Pax1 gene, as revealed by FISH analysis. However, mutation of the Pax1 gene is responsible for the un phenotype, but the Pax1 gene in the kkt mice is not rearranged or deleted. Pax1 is expressed normally in kkt embryos and in the thymus of mature animals, and there is no mutation in its coding sequence. Thus, the skeletal abnormalities observed in the kkt mutant are not due to a lack of functional Pax1. Mouse genomic sequences flanking the transgene and PAC clones spanning the wild-type kkt locus have been isolated, and reverse Northern analysis showed that the PACs contain transcribed sequence. Compound heterozygotes between un and kkt (un(+/-)/kkt(+/-)) display skeletal abnormalities similar to those of un or kkt homozygotes, but they have multiple lumbar vertebrae with a split vertebral body that is more severe than in homozygous un or kkt neonates. Furthermore, the sternebrae are not fused and no backward-pointing transverse processes are detected in L6. It is therefore apparent that these two mutations do not fully complement each other, and we propose that a gene in the kkt locus possesses a unique role that functions in concert with Pax1 during skeletal development.


Subject(s)
DNA-Binding Proteins/genetics , Mutation , Transcription Factors/genetics , Animals , Base Sequence , Bone and Bones/anatomy & histology , Chromosome Mapping , Cloning, Molecular , DNA Primers , Mice , Mice, Transgenic , Paired Box Transcription Factors , Phenotype
5.
Mater Med Pol ; 27(1): 11-3, 1995.
Article in English | MEDLINE | ID: mdl-8569269

ABSTRACT

Carcinoma of the gallbladder has always been associated with dismal prognosis. In this study we present single institution experience in surgical treatment for gallbladder cancer obtained during last five years. Even with recent improvement in diagnostic imaging modalities gallbladder malignancies are still diagnosed too late. The choice of operative procedure for a treatment of gallbladder carcinoma still remained the open question. Carcinoma of the gallbladder is not very common disease in Europe, but some how more common in Poland. According to the National Register, based on a study from 1991, 1863 cases of death from the gallbladder carcinomas were registered [13]. At the same time 2015 new cancer cases were diagnosed and registered. These gave us a crude rate of new cases in 1991 as follows: 2.7/100,000 man and 7.7/100,000 female. Those were even higher for some voivodeships in 1988, for example: Lódz (M = 3.95/100,000, F = 10.58/100,000) and Warsaw (M = 3.15/100,000, F = 7.59/100,000). Carcinoma of the gallbladder has always been associated with dismal prognosis. This was essentially the result of the slow and asymptomatic growth of the neoplasm that infiltrates the surrounding structures, such as the portal vein, hepatic artery and liver parenchyma, making a curative surgical treatment almost impossible. So there is a general impression that no progress has been made during last 20 years in the treatment for carcinoma of the gallbladder [2, 7, 9, 12]. However, in last years, we have observed improvements in diagnostic, surgical and intensive care techniques that allowed to offer a wider range of surgical and non-surgical options to our patients [1, 3, 4, 6, 8].(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Carcinoma/surgery , Gallbladder Neoplasms/surgery , Adult , Age Distribution , Aged , Aged, 80 and over , Carcinoma/epidemiology , Carcinoma/mortality , Female , Gallbladder Neoplasms/epidemiology , Gallbladder Neoplasms/mortality , Humans , Incidence , Male , Middle Aged , Poland/epidemiology , Prognosis , Sex Distribution
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