Bone Abstracts

Brittle bones have been reported in children, adolescents and adults with cystic fibrosis (CF), independently of sex; this has been termed CF-related bone disease. In CF patients with the F508del mutation in the (Cftr) gene, vertebral fractures and the subsequent dorsal kyphosis decrease pulmonary function, thus accelerating the course of the disease. Mice with the homozygous F508del mutation in CFTR develop a severe osteopenic phenotype early on, in both sexes (Le He...

Purpose: Sclerostin, a Wnt inhibitor produced by osteocytes that regulate bone remodelling, might be involved in cartilage metabolism. Therefore, we assessed the effect of sclerostin in osteoarthritis using SOST-deficient mice.Methods: SOST-KO and wild type (WT) mice underwent partial meniscectomie (Mnx). Mice were sacrificed at 4, 6 or 9 weeks after Mnx to analyze i) bone volume (BV/TV) at the femoral condyle, ii) osteophyte volume (microCT), iii) carti...

see PP15....

Objective: Cartilage loss and subchondral bone changes are hallmarks of osteoarthritis (OA). The Wnt family is involved in the regulation of bone and cartilage. We have shown that the Wnt/β-catenin pathway is activated in bone during OA, but the effect of its inhibition in bone in cartilage remodeling is unknown. We here investigated the impact of the bone-specific inhibition of Wnt during the development of OA.Methods: Partial meniscectomy (Mnx) wa...

Purpose: High osteoclastogenesis accompanies early stages of osteoarthritis (OA). Cartilage loss is reduced when osteoclasts are inhibited in mice models with bone hyperresorption. Although several evidences show that osteoclast-produced molecules affects chondrocyte metabolism, the mechanism by which inhibition of osteoclasts protects from cartilage damage is unclear. Our purpose was to investigate the role of Sphingosine 1 Phosphate, a lipid mediator secreted by osteoclasts ...

Increasing bone formation is an effective approach to prevent osteoporotic fractures. Although the intermittent administration of PTH is an established osteoanabolic therapy and an anti-Sclerostin antibody (Scle-AB) is currently being tested in phase 3 clinical trials, a great need exists for additional bone anabolic agents. Thus, in the context of a bi-national consortium we aim to uncover novel epigenomic networks controlling bone formation to identify new epigenomic approac...

Background: There are no models for estimating risk of fracture in patients taking treatments for osteoporosis. Knowing a patient’s risk of fracture during treatment may help make future treatment decisions; therefore, the development of on-treatment fracture risk models is needed.Methods: To assess on-treatment fracture risk, the analysis included subjects who received denosumab (DMAb) 60 mg Q6 every 6 months for at least 1 year in either FREEDOM o...

Introduction: The calcium sensing receptor presence (CaSR) at the surface of the osteocytes has never been clearly investigated. The CaSR are known to be express on osteoblasts. Osteocytes being old osteoblasts embedded in the matrix, this expression of CaSR is likely, and could constitute a key role to calcium signalling.Strontium ranelate (SrRan) has shown to activate osteoblasts by fixation on CaSR (Chattopadhyay N 2007, Biochem Pharmacol; Hu...

Objectives: Strong coordination between osteoblasts and bone marrow cells is fundamental for the regulation of healthy bone turnover and other (patho)physiological processes. Extracellular vesicles (EVs) mediate communication between cells via horizontal transfer of proteins and nucleic acids. Osteoblasts secrete EVs in the form of matrix vesicles involved in bone mineralization, however, information about a role in intercellular communication is still lacking. In this study, ...

Introduction: Umbilical cord blood (UCB) is increasingly used in hematopoietic stem cell (HSC) transplantations; however, the low cell numbers are still remaining as a limiting factor for proper engraftment. Osteoblasts are major constituents of HSC niche and play important roles in regulating HSC self-renewal and differentiation. Recently, extracellular vesicles (EVs) have been implicated in stem cell fate regulation via horizontal transfer of proteins and nucleic acids betwe...