Bone Abstracts

Background: We have previously shown that MLO-Y4 osteocytes express a number of P2 receptors, respond to a broad range of nucleotides (e.g. UTP) by increasing intracellular calcium concentration and release ATP upon both mechanical and UTP stimulation. The aim of this study therefore is to investigate how the osteocytes release ATP and whether there is a difference in release pathway depending on the type of stimulus.Methods: ATP release was investigated...

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...

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 ...

RANKL is the central player in the regulation of osteoclastogenesis and the quantity of RANKL presented to osteoclast precursors is an important factor determining the magnitude of osteoclast formation. It had been believed for years that osteoblastic cells are the major source of RANKL presented to osteoclast precursors, and we have previously focused on RANKL intracellular behavior in osteoblastic cells. However, recent two reports controverted this traditional concept and s...

The osteocyte most likely plays a role in bone remodeling by instructing osteoclasts to remove bone at specific sites. This entire process includes recruitment, proliferation and differentiation of osteoclast precursors. And osteocytes are responsible for detecting and responding to mechanical strain and may send signal to other cells. Therefore, to determine the role for osteocytes and mechanical strain in bone remodeling, we examined the effect of steady or pulsatile shear s...

The PTH type 1 receptor (PTH1R) is an important modulator of bone remodeling. In mice, PTH1R ablation in osteocytes produces trabecular bone reduction and impaired calcium homeostasis; meanwhile, its overexpression in these cells promotes periosteal and endocortical bone formation. Osteocytes can translate mechanical stimuli into bone-forming signals. Skeletal unloading induces osteocyte apoptosis and bone loss, whereas mechanical stimuli prevent osteocyte apoptosis through in...

It is hypothesized that osteocytes regulate bone adaptation by sensing mechanical strains in their microenvironments and signaling net bone formation or resorption. Owing to bone’s anisotropic architecture, individual osteocytes within a bone experience varying strains under mechanical loading. Thus, to accurately determine the relationships between mechanical strain, osteocyte behavior, and bone remodeling, it is crucial to use a single-cell approach. Using an in viv...

Strontium ranelate (SrRan) is an efficient treatment for osteoporosis, because SrRan both inhibits osteoclasts and stimulates osteoblastic bone formation. We have previously shown that SrRan also affects mouse osteocyte signaling towards osteoclast precursors and mature osteoblasts. This study assessed the effect of SrRan on paracrine signaling from mechanically-stimulated human osteocytes towards mesenchymal stem cells.Human primary bone cells, used as ...

Osteocytes differentiate from osteoblasts, are embedded in mineralised matrix and are critical regulators of bone remodelling. In vitro osteocyte models are limited to cell lines in monolayer, which do not represent their 3D environment in vivo. We have shown that osteoblasts in 3D gels differentiate along the osteocytic pathway. Since IGF1 regulates osteoblasts, and is involved in osteocyte response to mechanical loading, we hypothesised that IGF1 modulates ...

Osteocytes make up >90% of bone cells, are embedded in mineralised matrix where they form a communication network. Osteocytes differentiate from osteoblasts, and are mechano-sensitive. They are very difficult to isolate with a dependence on cell lines for in vitro studies of osteocyte biology. Therefore new methods to study these cells are essential. Recent publications indicate that osteoblasts maintained in in vitro 3D collagen gels may differentiate to...