Bone Abstracts

High fat diet (HFD), obesity, and physical inactivity characterize the modern lifestyle. This can lead to coronary heart diseases and type 2 diabetes mellitus. Recent studies have shown that these conditions frequently are associated with poor bone quality. However, the molecular mechanisms are poorly understood. To analyze the effect of HFD and exercise (EX) on bone homeostasis, we fed 6 week-old C57BL/6 mice a high fat (60% fat) or standard chow diet for 10 weeks (10-20 mice...

The pathogenesis of skeletal fragility in diabetes mellitus is poorly defined and efficient therapies are limited. Zucker diabetic fatty (ZDF) rats with type 2 diabetes mellitus display low bone mass and delayed bone defect healing. We tested whether intermittent treatment with human parathyroid hormone 1–84 (PTH) increases bone mass and bone defect regeneration in diabetic rats.A subcritical gap defect was created at the femur of 10 weeks old diabe...

Prostate cancer (PCa) is the most common cancer type in older men and often metastasizes to bone in advanced stages. Wnt proteins are implicated in carcinogenesis and especially WNT5A has been discussed to influence the clinical outcome of various cancer types, including PCa. In addition, WNT5A stimulates osteogenic differentiation and may thus not only be involved in PCa development, but also in the formation of subsequent skeletal metastasis. Here, we determined the role of ...

Bone fractures of patients suffering from type 2 diabetes mellitus (T2DM) represent an emerging socioeconomic problem. Underling mechanisms are poorly understood and therapies are limited. Our previous studies have shown that sulfated hyaluronan (sHA3) suppresses osteoclast activity while supporting osteoblast function in vitro. Hence, we now investigated if sHA3 can improve the delayed fracture healing in rats with T2DM.Porous, cross-linked lactide-base...

Introduction: Bone metastases represent a frequent complication of breast cancer and are characterized by increased tumour-driven activation of osteoclasts and subsequent bone loss. Aminobisphosphonates inhibit osteoclast function and are established therapies of skeletal metastases. Similar to statins, they block the mevalonate pathway and are thought to have direct anti-tumour effects. Here, we report on the anti-tumour potential of a sequential inhibition of the mevalonate ...

Bone remodeling is a crucial process to maintain a healthy bone structure in order to avoid diseases like osteoporosis or osteopetrosis. Osteoclasts contribute to this process by resorbing old and brittle bone allowing osteoblasts to renew the bone substance. During resorption osteoclasts rearrange their actin cytoskeleton by forming an F-actin ring generating a resorptive cavity on the bone surface. Recently, we reported that the F-actin binding protein SWAP-70 regulates oste...

Clinical data suggest that the mTOR inhibitor everolimus may have bone protective effects in addition to its anti-tumor effects in women with ER+/HER2− metastatic breast cancer receiving hormone-ablative therapies. Based on these findings, we tested the hypothesis, whether everolimus exerts concurrent anti-tumor effects while protecting the skeleton in murine models. Thus, we assessed bone metabolism and anti-tumor effects in osteolytic cancer models upon exposure to eve...

Iron overload due to hemochromatosis or chronic blood transfusions has been implicated in the development of osteoporosis. However, the impact of iron overload or iron deficiency on stromal cell functions and the underlying mechanisms are poorly defined. Since the Wnt signaling pathway is a critical regulator of bone remodelling, we aimed to analyse the effects of iron overload and iron deficiency on osteoblast function and further define the role of Wnt signaling in these pro...

Hyperthyroidism in mice is associated with a low bone mass, an increased bone turnover and high serum levels of sclerostin, a potent Wnt inhibitor. Here, we explored the effects of either reducing bone turnover with bisphosphonates or increasing bone formation with neutralizing sclerostin antibodies (Scl-Ab) on bone mass and estimated strength in hyperthyroid mice.Twelve-week-old C57BL/6 male mice were rendered hyperthyroid by adding L-thy...

Introduction: Collagen and glycosaminoglycans (GAGs) such as hyaluronan (HA) and chondroitin sulfate (CS) are basic elements of bone structure and collagen-GAG composites are currently developed for a wide range of applications. Here, we report on the molecular and cellular effects of GAGs and their sulfated derivatives on osteocytes, which are fundamental orchestrators of bone remodeling.Materials and methods: The effects of native and sulfate-modified ...