This minireview briefly surveys the complexity of regulations governing the bone metabolism. The impact of clinical studies devoted to osteoporosis is briefly summarized and the emphasis is put on the significance of experimental mouse models based on an extensive use of genetically modified animals. Despite possible arising drawbacks, the studies in mice are of prime importance for expanding our knowledge on bone metabolism. With respect to human physiology and medicine, one should be always aware of possib le limitations as the experimental results may not be, or may be only to some extent, transposed to humans. If applicable to humans, results obtained in mice provide new clues for assessing un foreseen treatment strategies for patients. A recent publication representing in our opinion the important breakthrough in the field of bone metabolism in mice is commented in detail. It provides an evidence that skeleton is endocrine organ that affects energy metabolism and osteocalcin, a protein specifically synthesized and secreted by osteoblasts, is a hormone involved. If confirmed by other groups and applicable to humans, this study provides the awaited connection of long duration between bone disorders on one hand and obesity and diabetes on the other., O. Raška, K. Bernášková, I. Raška Jr., and Obsahuje seznam literatury
Osteoporosis is a bone disease characterized by low bone mineral density (BMD) and impaired bone microarchitecture due to the abnormal activity of osteoclasts. Cathelicidins are antimicrobial peptides present in the lysosomes of macrophages and polymorphonuclear leukocytes. LL-37, a cathelicidin, induces various biological effects, including modulation of the immune system, angiogenesis, wound healing, cancer growth, as well as inflammation, and bone loss. A previous study reported direct involvement of LL-37 suppressing osteoclastogenesis in humans. Here, we examined the role of LL-37 in the treatment of osteoporosis using an ovariectomy (OVX) rat model. Our results showed that LL-37 significantly reduced bone loss and pathological injury in OVX rats with osteoporosis. Furthermore, we found that LL-37 significantly increased the activity of the Wnt/β-catenin pathway in OVX rats with osteoporosis, including the increased expression of β-catenin, Osterix (Osx), and Runt-related transcription factor 2 (Runx2), whereas XAV-939, an inhibitor of the Wnt/β-catenin pathway, significantly blocked the effects of LL-37 on bone loss and abnormal bone metabolism. Altogether, our findings suggested that LL-37 exerted a protective role in regulating bone loss and abnormal bone metabolism in rats with osteoporosis by activating the Wnt/β-catenin pathway.
No data are available about the effects of AT1 receptor antagonist losartan on the skeleton and there is also little information on the activity of an ACE inhibitor enalapril on bone metabolism. It is widely believed that the vasculature plays an important role in bone remodeling under normal and pathological conditions. We treated 14-week-old female Wistar rats with losartan, enalapril or saline. Administration of the ACE inhibitor enalapril and angiotensin II antagonist losartan had no effect on total malondialdehyde (MDA) in the blood and on urinary excretion of some eicosanoids and their metabolites. The administration of enalapril and losartan in a dose recommended for the treatment of hypertension did not cause significant changes in bone density, the ash and mineral content or morphometric parameters of the femur compared to the values found in control female rats., P. D. Broulík, V. Tesař, T. Zima, M. Jirsa., and Obsahuje bibliografii