Bone Abstracts

Introduction: One third of patients in the long-term heparin therapy show reduction in bone density. We have shown that heparin binds to bone morphogenetic protein 6 (BMP6) and inhibits its osteogenic activity in vitro. Here we explored whether heparin effects BMP6 mediated bone efficacy in vivo.Methods: We have used a mouse model of postmenopausal osteoporosis and tested the effect of heparin on BMP6 therapy and its osteogenic activity...

TSH exerts both antiresorptive and anabolic effects on bone remodeling in aged ovariectomized rats and TSH−/− mice, supported by clinical results demonstrating that low TSH level is associated with increased bone loss. To further explore the effect of TSH on bone metabolism we here introduced a rat model with removed thyroid and parathyroid glands to obtain low serum concentrations of thyroid and parathyroid hormone, calcitonin and 1,25(OH)2D<...

Reduced peripheral serotonin (5HT) in mice lacking tryptophan hydroxylase (TPH1), the rate limiting enzyme for 5HT synthesis, was reported to be anabolic to the skeleton. However, in other studies, TPH1 deletion either had no bone effect or an age-dependent inhibition of osteoclastic bone resorption. The role of 5HT in bone therefore remains poorly understood. To address this issue, we used selective breeding to create rat sublines with constitutively high (high-5HT) and low (...

Although bone morphogenetic protein 6 (BMP6) is known for its ability to induce growth of bone and cartilage, recent studies identified BMP6 as a key endogenous regulator of hepcidin expression and iron metabolism. Here, we examined BMP6 presence in the serum and investigated whether circulating levels of BMP6 may reflect body iron status. First, we showed by liquid chromatography–mass spectrometry (LC–MS) and western blotting that BMP6 is present in the circulation ...

High doses of BMPs are needed to achieve clinical success in bone fracture repair with currently available devices. BMP6 has a higher potency in stimulation of bone formation then its paralogue BMP7 due to less susceptibility to Noggin. The BMP6 carrier is a whole blood derived coagulum (WBCD) from the peripheral blood (OSTEOGROW). This WBCD, as an endogenous biocompatible material, significantly reduces the inflammatory response associated with current BMP-based treatments. M...

Bone morphogenetic protein 6 (BMP6) is a member of TGF-β superfamily with a high potential to induce new bone and cartilage. Here we demonstrate that BMP6 compared to the BMP7 paralog has unique biological properties. Previously, we showed that BMP6 is more active at lower amounts then BMP7 because of increased resistance to noggin due to lysine in position 60. Next, we discovered that BMP6 binds to blood coagulum components, which when modified with calcium salt and a fi...

Elevated levels of circulating serotonin have been reported to decrease bone mineral density1. Conversely, reduced serotonin (5HT) in mice lacking TPH1, the rate limiting enzyme for 5HT synthesis, was reported to be anabolic to the skeleton with high osteoblastic activity2. However, in other studies TPH1 deletion led to either an initial increase in BMD due to inhibition of osteoclastic bone resorption3, or had no bone effect4</su...

BMP6 is a member of the TGFβ superfamily with a high potential to induce new bone formation. Recently, we discovered that blood coagulum from the patient’s own blood (WBCD) modified with calcium salts serves as an appropriate autologous carrier for BMPs (OSTEOGROW device). Preclinical experiments indicate that BMP6 is efficacious when used in a significantly lower amounts than BMP2 and BMP7. Besides testing its osteogenic activity, we also tested the influence of the...

To further characterize the role of serotonin (5HT) in bone metabolism, Wistar-Zagreb rat model consisting of the high-5HT and low-5HT subline with different platelet 5HT content and transporter (5HTT) activity has been used.Primary osteoclasts from the high-5HT subline had an increased expression of 5HTT, 5HT–2A receptor, Trap and cathepsin K, while osteoblasts showed no difference in the expression of 5HT elements or osteoblastic markers. However,...