Bone marrow-derived mesenchymal cells and MMP13 contribute to experimental choroidal neovascularization.

in Cellular and Molecular Life Sciences : CMLS (2011), 68

In this study, we evaluate the potential involvement of collagenase-3 (MMP13), a matrix metalloproteinase (MMP) family member, in the exudative form of age-related macular degeneration characterized by a ... [more ▼]

In this study, we evaluate the potential involvement of collagenase-3 (MMP13), a matrix metalloproteinase (MMP) family member, in the exudative form of age-related macular degeneration characterized by a neovascularisation into the choroid. RT-PCR analysis revealed that human neovascular membranes issued from patients with AMD expressed high levels of Mmp13. The contribution of MMP13 in choroidal neovascularization (CNV) formation was explored by using a murine model of laser-induced CNV and applying it to wild-type mice (WT) and Mmp13-deficient mice (Mmp13 ( -/- ) mice). Angiogenic and inflammatory reactions were explored by immunohistochemistry. The implication of bone marrow (BM)-derived cells was determined by BM engraftment into irradiated mice and by injecting mesenchymal stem cells (MSC) isolated from WT BM. The deficiency of Mmp13 impaired CNV formation which was fully restored by WT BM engraftment and partially rescued by several injections of WT MSC. The present study sheds light on a novel function of MMP13 during BM-dependent choroidal vascularization and provides evidence for a role for MSC in the pathogenesis of CNV. [less ▲]

Bone Marrow-derived Myofibroblasts Are the Providers of Pro-invasive Matrix Metalloproteinase 13 in Primary Tumor.

in Neoplasia : An International Journal for Oncology Research (2012), 14(10), 943-51

Carcinoma-associated fibroblasts are key contributors of the tumor microenvironment that regulates carcinoma progression. They consist of a heterogeneous cell population with diverse origins, phenotypes ... [more ▼]

Carcinoma-associated fibroblasts are key contributors of the tumor microenvironment that regulates carcinoma progression. They consist of a heterogeneous cell population with diverse origins, phenotypes, and functions. In the present report, we have explored the contribution of bone marrow (BM)-derived cells to generate different fibroblast subsets that putatively produce the matrix metalloproteinase 13 (MMP13) and affect cancer cell invasion. A murine model of skin carcinoma was applied to mice, irradiated, and engrafted with BM isolated from green fluorescent protein (GFP) transgenic mice. We provide evidence that one third of BM-derived GFP(+) cells infiltrating the tumor expressed the chondroitin sulfate proteoglycan NG2 (pericytic marker) or alpha-smooth muscle actin (alpha-SMA, myofibroblast marker), whereas almost 90% of Thy1(+) fibroblasts were originating from resident GFP-negative cells. MMP13producing cells were exclusively alpha-SMA(+) cells and derived from GFP(+) BM cells. To investigate their impact on tumor invasion, we isolated mesenchymal stem cells (MSCs) from the BM of wild-type and MMP13-deficient mice. Wild-type MSC promoted cancer cell invasion in a spheroid assay, whereas MSCs obtained from MMP13-deficient mice failed to. Our data support the concept of fibroblast subset specialization with BM-derived alpha-SMA(+) cells being the main source of MMP13, a stromal mediator of cancer cell invasion. [less ▲]

Bone mineral density and health related quality of life: a 3-year follow-up study of osteoportic postmenopaul women

in The Open Geritric Medicine Journal (2009), 2

Objective: The objective of this study was to evaluate the relationship between change in bone mineral density (BMD) and change in health related quality of life (HRQoL) over a 3-year eriod, in patients ... [more ▼]

Objective: The objective of this study was to evaluate the relationship between change in bone mineral density (BMD) and change in health related quality of life (HRQoL) over a 3-year eriod, in patients without incident of osteoporotic fracture. Materials and Methods: Prior to the present study, two randomized controlled trials had been carried out to assess the efficacy of a new anti-osteoporotic drug. From the placebo group of those two trials, we selected for the present study 1838 osteoporotic postmenopausal women aged over 50 years, and followed their progress for a period of 3 years. BMD was measured at the lumbar spine and the proximal femur by dual-energy X-ray absorptiometry. Each patient received calcium and vitamin D supplements. HRQoL was assessed using 2 questionnaires: the generic tool Short Form 36 items (SF-36; including mental and physical components) and the specific Quality of Life Questionnaire in Osteoporosis (QUALIOST). Result: At baseline, after adjustment for body mass index (BMI), age, number of vertebral fractures and number of peripheral fractures, multivariate regression analysis showed a significant association between the lumbar BMD and the mental component of the SF-36 (p<0.001). However, the relationship was not significant with the global score of the QUALIOST (p=0.098) and the physical component of the SF-36 (p=0.051). Multivariate regressions did not show a significant relationship between HRQoL and proximal femur BMD at baseline. After 3 years of follow-up, multivariate regression analysis showed no significant association between change in lumbar BMD and the main HRQoL items (global score of the QUALIOST, physical and mental components of the SF-36; p between 0.437 and 0.942). No significant relationships were found between change in femoral BMD and change in the global score of the QUALIOST (p=0.088) or change in the mental component of the SF-36 (p=0.222). However, a significant positive association (p=0.031) appeared between change in the physical component of the SF-36 and femoral BMD change. Conclusion: In osteoporotic postmenopausal women receiving calcium and vitamin D, few relationships were found between BMD and HRQoL. However, these results were not strong enough to indicate a real clinically interesting relationship between HRQoL and BMD. Other studies would need to be performed to verify these results. [less ▲]

Bone mineral density and vertebral fractures in women who have discontinued hormone replacement therapy: a retrospective population-based study

in Osteoporosis International (2003, November), 14(Suppl. 7), 67

Bone mineral density of the spine and the hip measured with dual energy X-ray absorptiometry: normal range and fracture threshold for western European (Belgian) postmenopausal females.

in Clinical Rheumatology (1995), 14(1), 68-75

Bone mineral density (BMD) of the spine and the different regions of interest (ROI) of the hip were measured by dual energy X-ray absorptiometry in 278 healthy Belgian postmenopausal women and 93 ... [more ▼]

Bone mineral density (BMD) of the spine and the different regions of interest (ROI) of the hip were measured by dual energy X-ray absorptiometry in 278 healthy Belgian postmenopausal women and 93 postmenopausal type I osteoporotic females in order to: a) determine the normal range for lumbar and hip BMD values; b) define an "hypothetical" fracture threshold in this population; c) determine the preferential region to be considered for clinical use in type I osteoporosis. In the normal subjects, there is a negative relationship (< 0.001) between age or time elapsed since menopause (Tm) and BMD measured at the level of the spine or at the ROI of the hip. For the spine, evidence of a curvilinear relationship was assessed. Regressions of BMD at the hip as a function of age or time elapsed since menopause, were best fitted by a linear relationship. In the population of postmenopausal women who have experienced a vertebral crush fracture, no relationships were observed between spine BMD and age or Tm but the osteoporotic women had a spine BMD significantly lower compared to age-matched normal controls: Z-score = -1.2 +/- 0.6 (mean +/- SD) (p < 0.0001). Fracture threshold calculated as the 90th percentile of spine BMD measured in osteoporotic patients was 0.840 g/cm2, corresponding to the mean value -1 SD for a population of women aged 51 years. [less ▲]

Bone Regeneration Using Porous Titanium Particles versus Bovine Hydroxyapatite: A Sinus Lift Study in Rabbits.

in Clinical Implant Dentistry & Related Research (2011)

Aim: The first objective of this study was to qualitatively and quantitatively assess the bone formation process, particularly the long-term behavior and three-dimensional volume stability of subsinusal ... [more ▼]

Aim: The first objective of this study was to qualitatively and quantitatively assess the bone formation process, particularly the long-term behavior and three-dimensional volume stability of subsinusal bone regeneration, using titanium (Ti) or bovine hydroxyapatite (BHA) granules, in a rabbit model. The second objective was to evaluate the effect of the hydration of the BHA particles with a therapeutic concentration of doxycycline solution on the osteogenesis and biomaterial resorption. Materials and Methods: Rabbits underwent a double sinus lift procedure using one of three materials: grade 1 porous Ti particles, BHA, or BHA hydrated with doxycycline solution (0.1 mg/ml) (BHATTC). Animals were sacrificed after 1 week, 5 weeks, or 6 months. Samples were analyzed using µCT and nondecalcified histology. Results: The materials used in each of the three groups allowed an optimal bone formation; bone quantities and densities were not statistically different between the three groups. At 6 months, more stable three-dimensional volume stability was found with Ti and BHATTC (p = .0033). At 5 weeks and 6 months, bone to material contact corroborating osteoconduction was significantly higher with BHA and BHATTC than with Ti (p < .0001). Conclusions and Clinical Implications: Even though the studied biomaterials displayed different architectures, they are relevant candidates for sinus lift bone augmentation prior to dental implants because they allow adequate three-dimensional stability and osteogenesis. However, to recommend the clinical use of Ti, both an observation on the drilling effects of Ti particles and clinical trials are needed. [less ▲]

Bone remodelling after one-stage surgery implant placement in the posterior mandible

in Clinical Oral Implants Research (2005, September)

Bone resorption in post-menopausal women with normal and low BMD assessed with biochemical markers specific for telopeptide derived degradation products of collagen type I

in Calcified Tissue International (2001), 69(3), 130-137

Biochemical markers of bone resorption can be used clinically to predict the risk of osteoporosis-related fractures (prognostic tool) and to assess the response of an osteoporotic patient to an ... [more ▼]

Biochemical markers of bone resorption can be used clinically to predict the risk of osteoporosis-related fractures (prognostic tool) and to assess the response of an osteoporotic patient to an antiresorptive therapy (monitoring tool). Our aim was to assess the ability of four currently marketed biochemical markers of bone resorption, based on the measurement of degradation products from collage type I telopeptides to monitor the elevated resorption associated with menopause. Women (846) were stratified for menopause, age, and bone mineral density and the following markers were measured: urinary cross-linked N-telopeptides of type I collagen (NTx), the levels of breakdown products of type I collagen C-telopeptides in serum (S-CTx), and in urine, by ELISA (U-CTx-E), and RIA (U-CTx-R). Furthermore, the ratio (a/b) between the aL form of CTx measured in the CTx RIA and the bL form measured in the ELISA was calculated. The mean difference was calculated for each marker in women with osteopenia (Op) or osteoporosis (PMO) (WHO definition) compared with healthy premenopausal (Pre) women and postmenopausal (N Post) women with normal bone mass. Serum CTx showed the highest elevation in post- compared with premenopausal women. All marker values were significantly higher in Op and PMO subjects compared with both Pre and to N Post women. Compared with premenopausal values, the largest elevation in both Op and PMO women was observed for serum CTx. Compared with N Post, urine NTx showed the highest increase in OP subjects. The a/b CTx ratio was elevated in post- compared with Pre women, but there was no difference in the ratio among N Post, Op, or PMO women. In conclusion, postmenopausal women showed elevated turnover with all bone resorption markers, but with substantial individual variation in resorption levels. Furthermore, the turnover process in postmenopausal women appears to be quantitatively different from the premenopausal stage, apparent as altered a/b CTx ratios. [less ▲]

Bone resorption in postmenopausal women with normal and low BMD assessed with biochemical markers specific for telopeptide derived degradation products of collagen type I

in Clinical Rheumatology (2001), 5(Suppl.1), 427

Bone sialoprotein is expressed in both human neuroblastoma tissues and cell lines

in Proceedings of the American Association for Cancer Research (1998), 39