Imbalances in lipid metabolism affect bone homeostasis, altering bone mass and quality. A link between bone mass and high-density lipoprotein (HDL) has been proposed. Indeed, it has been recently shown that absence of the HDL receptor scavenger receptor class B type I (SR-B1) causes dense bone mediated by increased adrenocorticotropic hormone (ACTH). In the present study we aimed at further expanding the current knowledge as regards the fascinating bone-HDL connection studying bone turnover in apoA-1-deficient mice. Interestingly, we found that bone mass was greatly reduced in the apoA-1-deficient mice compared with their wild-type counterparts. More specifically, static and dynamic histomorphometry showed that the reduced bone mass in apoA-1 − / − mice reflect decreased bone formation. Biochemical composition and biomechanical properties of ApoA-1 − / − femora were significantly impaired. Mesenchymal stem cell (MSC) differentiation from the apoA-1 − / − mice showed reduced osteoblasts, and increased adipocytes, relative to wild type, in identical differentiation conditions. This suggests a shift in MSC subtypes toward adipocyte precursors, a result that is in line with our finding of increased bone marrow adiposity in apoA-1 − / − mouse femora. Notably, osteoclast differentiation in vitro and osteoclast surface in vivo were unaffected in the knock-out mice. In whole bone marrow, PPARγ was greatly increased, consistent with increased adipocytes and committed precursors. Further, in the apoA-1 − / − mice marrow, CXCL12 and ANXA2 levels were significantly decreased, whereas CXCR4 were increased, consistent with reduced signaling in a pathway that supports MSC homing and osteoblast generation. In keeping, in the apoA-1 − / − animals the osteoblast-related factors Runx2, osterix, and Col1a1 were also decreased. The apoA-1 − / − phenotype also included augmented CEPBa levels, suggesting complex changes in growth and differentiation that deserve further investigation. We conclude that the apoA-1 deficiency generates changes in the bone cell precursor population that increase adipoblast, and decrease osteoblast production resulting in reduced bone mass and impaired bone quality in mice.Laboratory Investigation (2016) 96, 763-772; doi:10.1038/labinvest.2016 published online 18 April 2016 Osteoporosis is characterized by low bone mass and microarchitectural deterioration of bone, resulting in bone fragility and fracture susceptibility. 1,2 It is a major public health problem worldwide; indeed, in the United States, more than 44 million people have osteoporosis or low bone mass. 3 The pathogenesis of osteoporosis is multifactorial. Age, sex, body size, metabolic factors, and genetic susceptibility are contributory factors. Interestingly, several studies have shown that there are strong links between bone, fat metabolism, and systemic energy metabolism, and that perturbations in lipid regulatory pathways may trigger both local and systemic phenomena that ultimately affect osteoblast and/or osteoclast function, resulting...
Titanium and its alloys are the most popular biomaterials replacing hard tissues in implant surgeries. Clinicians are generally pleased by titanium mechanical properties and non-toxicity performances; on the other hand, there have been reported several cases of titanium implantation failure, phenomenon explained sometimes as "non adherence of human tissue to the metallic surface." Yet, researchers reported that titanium surfaces are favorable for osteoblasts adhesion. Therefore, titanium integration into the human body remains an unsolved problem. In the present study, biocompatibility tests were performed on titanium and TiO(2) nanotubes substrates, involving human bone marrow cells. The combination of a newly developed analytical model based on the hybrid interphase concept, applicable to systems consisting of inert materials when in contact with living tissues, together with experimental results, confirmed previous research studies and lead to the conclusion that osteoblasts adhere efficiently to titanium surfaces. However, the present results suggest that osteoblasts strong anchorage at the very first moment of their contact with the metallic material leads to their apoptosis. It is most probable that in several cases this is the reason of failed implantation surgeries involving titanium.
Multiwalled carbon nanotubes (MWCNTs) are considered to be excellent reinforcements for biorelated applications, but, before being incorporated into biomedical devices, their biocompatibility need to be investigated thoroughly. We investigated the ability of films of pristine MWCNTs to influence human mesenchymal stem cells' proliferation, morphology, and differentiation into osteoblasts. Moreover, the selective integrin subunit expression and the adhesion mechanism to the substrate were evaluated on the basis of adherent cell number and adhesion strength, following the treatment of cells with blocking antibodies to a series of integrin subunits. Results indicated that MWCNTs accelerated cell differentiation to a higher extent than tissue culture plastic, even in the absence of additional biochemical inducing agents. The pre-treatment with anti-integrin antibodies decreased number of adherent cells and adhesion strength at 4-60%, depending on integrin subunit. These findings suggest that pristine MWCNTs represent a suitable reinforcement for bone tissue engineering scaffolds.
The underlying mechanisms by which bone cells respond to mechanical stimuli or how mechanical loads act on osteocytes housed in lacunae in bone are not well understood. In this study, a multilevel finite element (FE) approach is applied to predict local cell deformations in bone tissue. The local structure of the matrix dictates the local mechanical environment of an osteocyte. Cell deformations are predicted from detailed linear FE analysis of the microstructure, consisting of an arrangement of cells embedded in bone matrix material. This work has related the loads applied to a whole femur during the stance phase of the gait cycle to the strain of a single lacuna and of canaliculi. The predicted bone matrix strains around osteocyte lacunae and canaliculi were nonuniform and differed significantly from the macroscopically measured strains. Peak stresses and strains in the walls of the lacuna were up to six times those in the bulk extracellular matrix. Significant strain concentrations were observed at sites where the process meets the cell body.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.