Barriers and solutions to osteoporosis care in patients with a hip fracture.
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Education, Medical, Continuing↗
Biomedical subjects
Mark E Bolander
Publications and source records attributed to Mark E Bolander.
The human homolog of yeast SEP1 is a novel candidate tumor suppressor gene in osteogenic sarcoma.
The hSEP1 gene is the human homolog of yeast SEP1. Yeast SEP1 is a multifunctional gene that regulates a variety of nuclear and cytoplasmic functions including homologous recombination, meiosis, telomere maintenance, RNA metabolism and microtubule assembly. The function of hSEP1 is not known. We show loss or reduced expression of hSEP1 messenger RNA (mRNA) in three of four primary osteogenic sarcoma (OGS)-derived cell lines and in eight of nine OGS biopsy specimen. In addition, we find a heterozygous missense mutation (Valine(1484)>Alanine) at a conserved amino acid in the primary OGS-derived cell line U2OS. Importantly, we identified a homozygous missense mutation involving a CG-dinucleotide leading to a change in a conserved amino acid, aspartic acid(1137) >asparagine, in the primary OGS-derived cell line, TE85. hSEP1 mRNA expression was nearly undetectable in TE85 and low in U2OS cell lines. None of these mutations were identified in 20 normal samples consisting of bone, cartilage and fibroblast. The hSEP1 gene is located in chromosome 3 at 3q25-26.1 between markers D3S1309 and D3S1569. An adjacent locus defined by the polymorphic markers D3S1212 and D3S1245 has previously been reported to undergo loss of heterozygosity (LOH) at a >70% frequency in OGS and claimed to harbor an important tumor suppressor gene in osteosarcoma. The homozygous mutation in the hSEP1 mRNA in TE85 cell line suggest that this gene itself is subject to LOH. Taken together, these results suggest that hSEP1 acts as a tumor suppressor gene in OGS.
Base Sequence↗
Further characterization of human fetal osteoblastic hFOB 1.19 and hFOB/ER alpha cells: bone formation in vivo and karyotype analysis using multicolor fluorescent in situ hybridization.
We have previously generated an immortalized human fetal osteoblastic cell line (hFOB) using stably transfected temperature sensitive SV40 T-antigen (Harris et al. [1995a] J. Bone. Miner. Res. 10:178-1860). To characterize these cells for phenotypic/genotypic attributes desired for a good cell model system, we performed karyotype analysis by multicolor fluorescent in situ hybridization (M-FISH), their ability to form bone in vivo without developing cell transformation, and finally their ability to form extracellular matrix formation in vitro. The karyotype analysis of hFOB cells revealed structural or numeric anomalies involving 1-2 chromosomes. In contrast, the human osteosarcoma MG63 cells displayed multiple, and often complex, numeric, and structural abnormalities. Subcutaneous injection of hFOB cells in the presence of Matrigel into nude mice resulted in bone formation after 2-3 weeks. Electron microscopic analysis of the extracellular matrix deposited by hFOB cells in culture revealed a parallel array of lightly banded fibrils typical of the fibrillar collagens such as type I and III. These results demonstrate that the hFOB cell line has minimal chromosome abnormalities, exhibit the matrix synthetic properties of differentiated osteoblasts, and are immortalized but non-transformed cell line. These hFOB cells thus appear to be an excellent model system for the study of osteoblast biology in vitro.
Animals↗
Calcium signaling is required for ultrasound-stimulated aggrecan synthesis by rat chondrocytes.
Low-intensity ultrasound accelerates fracture healing in humans. In rat femur fracture models, ultrasound advanced healing is associated with increased proteoglycan expression. Here we report that ultrasound stimulation of primary rat chondrocytes elevated the intracellular concentration of calcium [Ca2+]i. The [Ca2+]i increase was rapid and transient at lower pressures (175-320 kPa), but rapid and sustained at higher ultrasound exposures (350-500 kPa). Chelating internal [Ca2+]i with 1,2-bis(2-aminophenoxy) ethane-N-N-N',N'-tetraacetic acid (BAPTA-AM), stopping the Ca2+/ATP-ase induced mitochondrial release of [Ca2+]i with Thapsigargin, or removing [Ca2+]i from the medium with EGTA inhibited the stimulatory effects of ultrasound on proteoglycan synthesis. These results imply that ultrasound-stimulated synthesis of cell matrix proteoglycan, associated with accelerated fracture healing, is mediated by intracellular calcium signaling.
Aggrecans↗
The spatiotemporal expression of TGF-beta1 and its receptors during periosteal chondrogenesis in vitro.
Transforming growth factor-beta1 (TGF-beta1) has been shown to stimulate chondrogenesis in periosteal explants cultured in agarose suspension. TGF-betas exert their cellular effects through a heteromeric cell membrane receptor complex consisting of TGF-beta type I and type II receptors. In this study, the spatial and temporal expressions of the type I receptor (TbetaR-I), type II receptor (TbetaR-II) and endogenous TGF-beta1 in periosteal explants cultured in vitro were examined using reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry. The temporal changes in the expression of the TbetaR-I and TbetaR-II mRNAs correlated with that of TGF-beta1. Exogenous administration of TGF-beta1 upregulated the expression of both receptors and of the TGF-beta1 ligand in a biphasic pattern. The earlier peak of upregulation was observed at 7 days in culture. A later peak of upregulation was seen at 42 days, at which time cartilage formation reached a maximum. Immunohistochemical studies demonstrated co-localization of TbetaR-I and TbetaR-II simultaneously among the same cells expressing TGF-beta1. TGF-beta1 treatment increased the expression of TGF-beta1, TbetaR-I and TbetaR-II in mesenchymal cells in the cambium layer at 7 days in culture. Small round chondrocytes showed widely distributed immunoreactivity of TGF-beta1, TbetaR-I and TbetaR-II in the 42-day explants treated with TGF-beta1. These observations support the hypothesis that TGF-beta1 regulates the initiation and formation of cartilage during periosteal chondrogenesis.
Activin Receptors, Type I↗
Primer on medical genomics. Part III: Microarray experiments and data analysis.
Genomics has been defined as the comprehensive study of whole sets of genes, gene products, and their interactions as opposed to the study of single genes or proteins. Microarray technology is one of many novel tools that are allowing global and high-throughput analysis of genes and gene products. In addition to an introduction on underlying principles, the current review focuses on the use of both complementary DNA and oligodeoxynucleotide microarrays in gene expression analysis. Genome-wide experiments generate a massive amount of data points that require systematic methods of analysis to extract biologically useful information. Accordingly, the current educational communication discusses different methods of data analysis, including supervised and unsupervised clustering algorithms. Illustrative clinical examples show clinical applications, including (1) identification of candidate genes or pathological pathways (ie, elucidation of pathogenesis); (2) identification of "new" molecular classes of diseases that may be relevant in disease reclassification, prognostication, and treatment selection (ie, class discovery); and (3) use of expression profiles of known disease classes to predict diagnosis and classification of unknown samples (ie, class prediction). The current review should serve as an introduction to the subject for clinician investigators, physicians and medical scientists in training, practicing clinicians, and other students of medicine.
Breast Neoplasms↗
Alumina-on-alumina total hip arthroplasty: a minimum 18.5-year follow-up study.
BACKGROUND: The purpose of this retrospective study was to report the results, after a minimum of 18.5 years of follow-up, in a consecutive series of total hip arthroplasties performed with an alumina-on-alumina combination. METHODS: One hundred and eighteen consecutive total hip arthroplasties were performed in 106 patients between 1979 and 1980. The prostheses combined a 32-mm alumina head and an all-alumina socket. Both components were cemented in eighty-five hips, both components were implanted without cement in twenty-nine, and only the stem was cemented in four. The mean age of the patients at the time of the index arthroplasty was 62.2 years (range, thirty-two to eighty-nine years). RESULTS: At the 18.5 to 20.5-year follow-up evaluation, forty-five patients (fifty-one hips) were alive and had not had a revision, twenty-five patients (twenty-five hips) had undergone revision of one or both components, twenty-seven patients (thirty hips) had died, and nine patients (twelve hips) had been lost to follow-up. The mean Merle d'Aubigné hip score (and standard deviation) was 16.2 +/- 1.8 points at the latest follow-up evaluation. The rate of survival at twenty years, with revision for any reason as the end-point, was 85.6% for the cementless cups compared with 61.2% for the cemented cups and 84.9% for the cementless stems compared with 87.3% for the cemented stems. Wear of the prosthetic components was undetectable on plain radiographs. Periprosthetic cystic or scalloped lesions requiring the use of allograft bone during revision were present in three of the twenty-five revised hips. In addition, seven hips had moderate acetabular osteolysis treated with a 4-mm-larger cup. No fracture of the alumina socket or head was recorded. The mean acetabular wear rate in this series was <0.025 mm/yr. CONCLUSION: With the alumina-on-alumina total hip arthroplasty, minimal wear rates and limited osteolysis can be expected up to twenty years after the operation, provided that sound acetabular component fixation is obtained.
Adult↗