| 1. |
- Brändström, Helena, et al.
(författare)
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Regulation of osteoprotegerin mRNA levels by prostaglandin E2 in human bone marrow stroma cells.
- 1998
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Ingår i: Biochemical and biophysical research communications. - : Elsevier BV. - 0006-291X. ; 247:2, s. 338-41
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Tidskriftsartikel (refereegranskat)abstract
- The recently cloned osteoclastogenesis inhibitory factor, or osteoprotegerin (OPG), has been shown to be a potent inhibitor of osteoclast formation. The inhibition is believed to be mediated through specific binding of OPG to a cell surface ligand on osteoblastic stromal cells. In this report we have studied the effect of the bone resorbing agent prostaglandin E2 (PGE2) on OPG mRNA levels in primary cultures of human bone marrow stroma cells (hBMSC). PGE2 dose- and time-dependently down-regulated the mRNA levels of OPG, as measured by RNAse protection assay. After 4 hours of stimulation with 1 microM PGE2, OPG mRNA levels were significantly decreased. The inhibitory effect was seen at and above 1 nM of PGE2. To elucidate whether the OPG mRNA levels are regulated via the proteinkinase A and/or the proteinkinase C pathways we stimulated cells with either forskolin (FSK) or phorbolic ester (PDbu) respectively. FSK (10 microM) decreased OPG mRNA levels to 50 % of control, whereas PE (10 nM) upregulated the mRNA levels to 250 % of control. These data show that PGE2 down-regulates the expression of OPG mRNA in hBMSC, probably via an increase in cAMP. This mechanism might be involved in PGE2-induced bone resorption.
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| 2. |
- Grundberg, Elin, et al.
(författare)
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A TA-repeat polymorphism in the gene for the estrogen receptor alpha does not correlate with muscle strength or body composition in young adult Swedish women.
- 2005
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Ingår i: Maturitas. - 0378-5122. ; 50:3, s. 153-60
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: There are conflicting data in the literature whether estrogens affect muscle strength. Prospective studies with hormone replacement therapy have not been able to convincingly demonstrate a muscular effect and the putative role of estrogen in the development of lean body mass is not established. Both lean mass and fat mass are known to be under strong genetic control and therefore we have investigated the relation between a TA-repeat in the gene for the estrogen receptor alpha (ERalpha) and muscle strength and body composition. METHODS: 175 healthy Swedish women, aged 20-39 were randomly selected from the population registry and included in the study. Body mass measurements (lean mass, fat mass, body weight and BMI) and muscle strength (quadriceps, hamstring and grip strength) were evaluated. The TA-repeat in the ERalpha gene was amplified by polymerase chain reaction. RESULTS: Alleles with a TA-repeat length of 16 repeats or shorter were denoted short (e), and repeat length of 17 repeats or longer were denoted long (E). Women homozygous for the short and long genotype were denoted ee (31%) and EE (21%), respectively, while heterozygous individuals were denoted Ee (48%). The frequencies were in Hardy-Weinberg equilibrium. No associations were found between ERalpha genotypes and muscle strength or body composition. CONCLUSION: The TA-repeat in the human ERalpha gene does not correlate with muscle strength or body mass measurements, indicating that body composition is not as sensitive to genetic variation in this receptor as other target organs for estrogen.
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| 3. |
- Grundberg, Elin, et al.
(författare)
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Vitamin D receptor 3' haplotypes are unequally expressed in primary human bone cells and associated with increased fracture risk: the MrOS Study in Sweden and Hong Kong.
- 2007
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Ingår i: Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. - : Wiley. - 0884-0431. ; 22:6, s. 832-40
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Tidskriftsartikel (refereegranskat)abstract
- The VDR is a prime candidate gene for osteoporosis. Here, we studied three common VDR haplotypes in relation to bone phenotypes in 5014 participants of the global MrOS Study. We also studied the relative expression of the haplotypes in human bone cells. One haplotype was associated with increased fracture risk and differently expressed in primary human bone cells. INTRODUCTION: Vitamin D plays an essential role in skeletal metabolism by binding to its nuclear steroid receptor, the vitamin D receptor (VDR). The heritability of BMD is well established, and the VDR gene is considered a prime candidate suggested to partially account for genetically controlled BMD variance in the population. MATERIALS AND METHODS: Here, we reconstructed common haplotypes in the VDR 3' untranslated region (UTR) and studied the association to BMD and risk of vertebral fractures in elderly men from Sweden (n = 3014) and Hong Kong (n = 2000), all participants of the global MrOS Study. To assess any functional implications of the VDR polymorphisms, we studied allele-specific expressions of the different VDR 3' UTR haplotypes in the normal chromosomal context of 70 unrelated human trabecular bone samples. This was performed by quantitative genotyping of coding polymorphisms in RNA samples and in corresponding DNA samples isolated from the bone samples. RESULTS: Three major haplotypes were reconstructed and in agreement with the previously well-defined baT, BAt, and bAT haplotypes, herein denoted Hap1, Hap2, and Hap3. The Hap1 haplotype was independently associated with increased risk of vertebral fractures in Swedish men (OR, 1.655; 95% CI, 1.146-2.391; p < 0.01) and with lower lumbar spine BMD in elderly men from Sweden (p < 0.01) and Hong Kong (p < 0.05). The VDR gene was also shown to exhibit a 3' UTR haplotype dependent allelic imbalance, indicating that the VDR Hap1 allele was overexpressed in human trabecular bone samples. CONCLUSIONS: The results indicate that the relatively overexpressed VDR Hap1 haplotype could be considered a risk allele for osteoporosis regardless of ethnicity.
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| 4. |
- Penno, Hendrik, et al.
(författare)
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Expression of RANK-ligand in prostate cancer cell lines
- 2009
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Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation. - : Informa UK Limited. - 0036-5513 .- 1502-7686. ; 69:1, s. 151-155
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Tidskriftsartikel (refereegranskat)abstract
- The molecular mediators of bone remodelling, receptor activator of nuclear factor-kappaB ligand (RANKL), receptor activator of nuclear factor-kappaB (RANK) and osteoprotegerine (OPG), are believed to be involved in the cellular mechanisms by which tumours metastasize to bone. RANKL is a potent stimulator of osteoclastic bone resorption and is expressed in a variety of tumour cells. We have investigated if the membrane bound form of RANKL is expressed in prostate cancer cell lines, and whether this expression might be regulated by the presence of human osteoblasts. Three prostate cancer cell lines were co-cultured with human osteoblast-like cells (hOB) and RANKL expression on cell surface was measured by FACS. We found basal expression of RANKL on the cell surface, and in co-culture with hOBs the number of cells expressing RANKL was increased between 2.5 and 4 times. These data suggest a signalling mechanism between bone cells and prostate cancer cells that might increase bone resorption and thereby promote bone metastases.
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