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
Bone remodeling is a tightly coupled process consisting of repetitive cycles of bone resorption and formation. Both processes are governed by mechanical signals, which operate in conjunction with local and systemic factors in a discrete anatomic structure designated a basic multicellular unit (BMU). The microenvironment around total joint arthroplasty is a dynamic and complex milieu influenced by the chemical and physical stimuli associated with servicing the prosthesis. A key factor limiting the longevity of the prosthesis is polyethylene wear, which induces particle disease, and this may lead to increased and prolonged activity of BMUs resulting in periprosthetic osteolysis. Several pathways regulating BMU function have been reported in the past, including RANKL/RANK/OPG/TRAF6, TNF-α/TNFR/TRAF1, and IL-6/CD126/JAK/STAT. Moreover, the expression and functional activity of all these molecules can be affected by variations in their genes. These may explain the differences in severity of bone defects or prosthetic failure between patients with similar wear rates and the same prosthesis. Simultaneously, this data strongly support the theory of individual susceptibility to prosthetic failure., J. Gallo, M. Raška, F. Mrázek, M. Petřek., and Obsahuje bibliografii a bibliografické odkazy
MicroRNAs (miRNAs) play vital roles in bone metabolism and participate in the mechanically induced bone alterations. The underlying molecular mechanisms by which fluid shear stress (FSS) regulate the proliferative and apoptotic phenotypic changes of osteoblasts remain elusive. The study aimed to investigate the regulatory effects of FSS on osteoblast proliferative and apoptotic phenotypes and the roles of miR-214-3p-ATF4 (activating transcription factor 4) signaling axis in the mechanomodulation processes. FSS promoted the proliferative activity of osteoblasts and suppressed mitochondrial-mediated osteoblast apoptosis. FSS decreased miR-214-3p expression and increased ATF4 expression in MC3T3-E1 osteoblasts. MiR-214-3p inhibited osteoblast proliferative activity and promoted mitochondrialmediated osteoblast apoptosis. Overexpression of miR-214-3p attenuated FSS-enhanced osteoblast proliferation and FSS-suppressed mitochondrial-mediated osteoblast apoptosis. We validated that ATF4 acted as a target gene of miR-214-3p. Moreover, miR-214-3p regulated osteoblast proliferation and apoptosis through targeting ATF4. Taken together, our study proved that FSS could suppress mitochondrial-mediated osteoblast apoptosis and promote osteoblast proliferation through the miR-214-3p-ATF4 signaling axis.
Spinal deformities such as scoliosis and kyphosis are incurable, and can lead to decreased physical function, pain, and reduced quality of life. Despite much effort, no clear therapies for the treatment of these conditions have been found. Therefore, the development of an animal model for spinal deformity would be extremely valuable to our understanding of vertebral diseases. In this study, we demonstrate that mice deficient in the mitochondrial enzyme isocitrate dehydrogenase 2 (IDH2) develop spinal deformities with aging. We use morphological analysis as well as radiographic and micro-CT imaging of IDH2-deficient mice to characterize these deformities. Histological analysis showed increased abnormalities in IDH2-deficient mice compared to wild type mice. Taken together, the results suggest that IDH2 plays a critical role in maintaining the spinal structure by affecting the homeostatic balance between osteoclasts and osteoblasts. This indicates that IDH2 might be a potent target for the development of therapies for spinal deformities. Our findings also provide a novel animal model for vertebral disease research., U. Chae, N.-R. Park, E. S. Kim, J.-Y. Choi, M. Yim, H.-S. Lee, S.-R. Lee, S. Lee, J.-W. Park, D.-S. Lee., and Obsahuje bibliografii
This comparative study of various surface treatments of commercially available implant materials is intended as guidance for orientation among particular surface treatment methods in term of the cell reaction of normal human osteoblasts and blood coagulation. The influence of physicochemical surface parameters such as roughness, surface free energy and wettability on the response of human osteoblasts in the immediate vicinity of implants and on the blood co agulation was studied. The osteoblast proliferation was monitored and the expression of tissue mediators (TNF-α , IL-8, MMP-1, bone alkaline phosphatase, VCAM-1, TGF-β ) was evaluated after the cell cultivation onto a wide range of commercially available materials (titanium and Ti6Al4V alloy with various surface treatments, CrCoMo alloy, zirconium oxide ceramics, polyethylene and carbon/carbon composite). The formation of a blood clot was investigated on the samples immersed in a freshly drawn whole rabbit blood using scanning electron microscope. The surfaces with an increased osteoblast proliferation exhibited particularly higher surface roughness (here Ra > 3.5 μm) followed by a high polar part of the surface free energy whereas the effect of wettability played a minor role. The surface roughness was also the main factor regulating the blood coagulation. The blood clot formation analys is showed a rapid coag ulum formation on the rough titanium-based surfaces. The titanium with an etching treatment was considered as th e most suitable candidate for healing into the bone tissue due to high osteoblast proliferation, the highest production of osteogenesis markers and low production of inflammatory cytokines and due to the most intensive blood clot formation., D. Kubies ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy