Volume 9 · Number 1 · March 2017
- Divergent effects of vascular endothelial growth factor, VEGF and the N-terminal fragment of the parathormone-related protein, PTHrP on human adipose derived from mesenchymal stem cells [3-4]
- Vascular endothelial growth factor (VEGF) and the N-terminal portion of parathyroid hormone-related protein (PTHrP) regulate the proliferation of human mesenchymal stem cell [5-12]
- Effects of the catalase antioxidant enzyme in vascular calcification and bone demineralization [13-19]
- Influence of obesity on microarchitecture and biomechanical properties in patients with hip fracture [20-27]
- Identification of genetic variants associated with bone mineral density (BMD) in the FLJ42280 gene [28-34]
- Mesenteric panniculitis associated with the use of bisphosphonates: are these more proinflammatory than we know? [35-37]
Divergent effects of vascular endothelial growth factor, VEGF and the N-terminal fragment of the parathormone-related protein, PTHrP on human adipose derived from mesenchymal stem cells
The possibility of obtaining stem cells from adult tissues is highly attractive as they can potentially generate a variety of differentiated cells and be used in tissue regeneration. The study of stem cells obtained from adult organisms began some 50 years ago, when hematopoietic stem cells were described, which give rise to all blood cells1. Later, researchers described mesenchymal lineage stem cells and differentiated them into adipocyte, osteoblastic and chondrocytic cells. Mesenchymal stem cells were originally discovered in bone marrow, but were later found in other adult tissues, including peripheral adipose tissue. As Bravo et al.2 report in their study, mesenchymal cells are characterized by the expression of surface markers, including CD90, and the use of others, such as CD45 and CD34.
Vascular endothelial growth factor (VEGF) and the N-terminal portion of parathyroid hormone-related protein (PTHrP) regulate the proliferation of human mesenchymal stem cells
Adipose tissue contains a large number of mesenchymal stem cells (ASCs) residing in their vascular stroma. Although there is controversy regarding the ability to generate bone tissue from these cells in vivo, the in vitro cells offer a good model of osteogenic differentiation due to its phenotypic similarity with the bone marrow stromal cells (BMSCs) in culture. The differentiation of osteo-progenitor populations of bone marrow is intensely regulated by local factors, such as vascular endothelial growth factor (VEGF) and parathyroid hormone-related protein (PTHrP), which modulate these populations’ proliferation in different stages of differentiation. Both the VEGF and the N-terminal fragment of the PTHrP exert osteogenic effects. In this study, we posited that its effects on proliferation of osteo-progenitors are stage dependent of osteoblastic differentiation. After confirming its capacity to in vitro differentiation by Runx2 gene expression and accumulation of calcium, the proliferative response to stimuli was analyzed with VEGF or PTHrP (1-36) of ASCs submitted or not to osteogenic induction. VEGF, but not PTHrP (1-36), stimulated the proliferative capacity of uninduced ASCs, whereas BMSCs, but not VEGF, stimulated the proliferation of induced ASCs, corroborating the differential role of this growth in different stages of differentiation.
Objetives: Assess the role of the catalase antioxidant enzyme in the vascular calcification process associated with chronic renal failure (CRF) and its effect on bone mass.
Material and methods: Wild type C57/BL6J mice (WT) and transgenic mice (TG) were used, that overexpress the catalase enzyme, to which CRF was induced. Control WT and TG mice were used in simulated intervention. After 16 weeks, the mice were sacrificed, with serum samples taken for biochemical markers as well as residual pieces of kidney, aorta and tibias. An in vitro model of primary culture of smooth vascular muscle cells (SVMC) taken from the WT and TG aorta which underwent eight days of 3 mM phosphorus and 2 mM calcium calcifying medium.
Results: A significant increase in Runx2 gene expression, calcium renal deposit and bone structure deterioration at trabecular level was only detected in WT mice with CRF. This was not observed in TG mice with CRF.
Only in the case of WT mice SVMC, did added calcification medium raise calcium levels, proteic Runx2 expression and the reactive oxygen species of mitochondria with low catalase enzyme.
Conclusions: Calcifying catalase over-expression was observed in both in vivo and in vitro, with in vivo showing that this reduction was accompanied by an improvement in bone parameters under study.
Influence of obesity on microarchitecture and biomechanical properties in patients with hip fracture
Introduction: Obesity and osteoporosis (OP) are two very prevalent diseases in our society today. The effect of obesity on bone quality is currently a subject under discussion.
Objective: To assess the effect of body weight on the microstructure and biomechanical properties of trabecular bone biopsies from the proximal end of the femur in patients with hip fracture fragility.
Material and Methods: Cross-sectional study of 16 patients with hip fracture. The 2 groups are divided according to their BMI: (A) normal weight individuals and (B) those with obesity. We collected biopsies of cancellous bone from the femoral head and assessed biochemical determinations (PTH, 25 (OH) vitamin D and IGF-1), bone remodeling markers (PINP, CTX), bone mass (BMD neck and total hip), bone microstructure and biomechanical study (µCt). Statistical analysis: Student’s t test (SPSS 22.0) significance p<0.05. Results: All patients had hip BMD in osteoporotic range. The obese group had higher levels of PTH and lower IGF-1, vitamin D and PINP. We found no differences in the parameters related to bone metabolism. The obese group showed better indices reaching microstructural significance: increased bone volume (BV/TV: 36.6±12.7 vs 19.4±11.4%, BS/TV: 5.5±1.1 vs 3.9±1.3%), higher trabecular number (Tb.N: 1.6±0.4 vs 1,01±0,4), greater trabecular width (Tb.Th: 0.22±0.003 vs 0.17±0.05) and lower trabecular separation (Tb.Sp: 0.51±0.12 vs 0.66±0.16). Biomechanical parameters confirm greater strength of trabecular bone in obese patients. Conclusion: Obesity may be a protective factor of bone quality in the femoral region and has less effect on bone mineral density.
FLJ42280 is a possible gene for susceptibility to osteoporosis. Different studies of GWAs have identified 4 non-coding SNPs in this gene associated with bone mineral density (BMD) and fracture risk.
In order to ascertain the cause of the association between these SNPs and osteoporosis, we searched for genetic variants by resequencing the 28-kb gene, in a truncated selection of women with very low (n=50) or very high BMD (N=50) of the BARCOS cohort (Barcelona Cohort Osteoporosis, cohort of postmenopausal women in Barcelona). The variants found were filtered and their frequency analyzed in each group.
The overlap of the variants with functional elements of the ENCODE project was calculated. Finally, an eQTL analysis of the 4 SNPs-coding was performed on the expression levels of FLJ42280 neighbor genes in lymphoblasts.
In all, 110 variants were selected. The differences in their frequencies between the two groups were below the statistical power of the experimental design. However, three variants overlapped with possible enhancers and one overlapped with an active enhancer in osteoblasts (rs4613908). A strong linkage disequilibrium was observed between the 4 non-coding SNPs and the SNP rs4613908, which belong to a block spanning the gene almost completely. None of the non-coding SNPs showed association with the expression levels of FLJ42280 neighbor genes.
In conclusion, the SNP rs4613908 could be involved functionally in determining BMD. Tangible experiments will be required to confirm this.
Mesenteric panniculitis associated with the use of bisphosphonates: are these more proinflammatory than we know?
Mesenteric panniculitis is characterized by chronic inflammation of the adipose tissue of the intestinal mesentery, and its etiology is unknown. It has been associated with malignancy, vasculitis, rheumatic diseases and the use of certain drugs. We present a case of panniculitis associated with bisphosphonate use, not previously described in the literature, thus suggesting its potential secondary proinflammatory effects.
Osteoporosis is a systemic skeletal disease characterized by low bone mineral density, changes in bone microarchitecture and increased risk of fracture. It has been shown that depends on physiological processes and secondary to other pathologies and associated with the use of glucocorticoids, the latest being the most common cause of osteoporosis associated to drugs, this may be represent a great magnitude public health issue. This review is presented in order to emphasize the clinical importance of osteoporosis in rheumatic diseases and glucocorticoid-induced osteoporosis.