Bone Abstracts

Bone has recently emerged as a novel endocrine organ regulating glucose metabolism. Ectonucleotide pyrophosphatase/phosphodiesterase-1 (NPP1) controls bone mineralisation by generating the mineralisation inhibitor pyrophosphate. In clinical studies increased activity of NPP1 has been found in patients with insulin resistance, and it has been shown to directly inhibit the insulin receptor. We hypothesised that mice lacking NPP1 (Enpp1−/−) would exhibit im...

Genetic approaches to bone physiology utilising judicious gain and loss of function models have identified bone as an endocrine organ, being involved in the regulation of energy metabolism and reproduction. Recent advances expand our understanding and identify a new and unconventional role of bone beyond its classical functions. PHOSPHO1 is a bone specific phosphatase with a recognised role in bone mineralisation, but our present studies have now identified a novel role for PH...

A major limitation in the development of cellular therapies using human mesenchymal stem cells (hMSCs) is cell survival post-transplantation. In this study, we challenged the current paradigm of hMSC survival, which assigned a pivotal role to oxygen, by testing the hypothesis that exogenous glucose may be key to hMSC survival. We demonstrated that hMSCs could endure sustained near-anoxia conditions only in the presence of glucose. In this in vitro cell model, the prot...

An IgM monoclonal gammopathy (MGUS) is often the first sign of a lymphomonocytic B-lymphoma (Waldenström macroglobulinemia-WD). Osteolytic lesions can occur in B cell malignancies (WD, hairy cell leukemia, LLC\..) but are less frequent than in myeloma. In addition, bone remodeling in WD is poorly understood. However, an osteoporosis is often observed in MGUS patients. We studied a series of bone biopsies performed in patients with an IgM gammopathy by histomorphometry, mi...

Anorexia nervosa (AN) a condition of profound undernutrition, is characterized by alterations in neuroendocrine and metabolic functions. Among the serious pathological consequences of this eating disorder, osteoporosis is often observed and persists after recovery, leading to a high fracture risk.To study particularly bone alterations and recovery, a long term mouse model has been developed. In this model named separation-based anorexia (SBA) – a ch...

Existence of inflammatory osteoclasts (iOCLs) contributing to pathological bone resorption associated with inflammatory diseases has been suspected for many years. However, specific markers of iOCLs are lacking, making impossible to establish the contribution of iOCLs to such pathologies. Whereas in steady state OCLs derive from monocytes (MN-OCLs), in inflammatory conditions, they also differentiate from dendritic cells (DC-OCLs). We recently showed that these 2 OCL populatio...

Tissue healing/reconstruction as well as exacerbated inflammatory diseases may benefit from stem cell based therapies. Ex vivo isolated tissue mesenchymal stromal cells (MSCs) displaying multi-potent activity and immune-regulatory functions were long ago proposed as therapeutic cells and already tested in many clinical assays. Nevertheless, their use may be restricted because of the few number that can be recovered from adult tissues, their limited in vitro e...

Chronic inflammatory diseases are characterized by a bone destruction mediated by an increased osteoclast (OCL) activity. OCLs are phagocytic cells arising from the myeloid lineage. Indeed, OCLs derive from monocytes (MN-OCLs) and, in an inflammatory context, they also derive from dendritic cells (DC-OCLs). Despite this origin, their role in the immune responses is still unclear. OCLs in steady state have been reported to act as antigen-presenting cells that activate CD8+...

Tissue healing/reconstruction as well as exacerbated inflammatory diseases may benefit from stem cell based therapies. Ex vivo isolated tissue mesenchymal stromal cells (MSCs) displaying multi-potent activity and immune-regulatory functions were long ago proposed as therapeutic cells and already tested in many clinical assays. Nevertheless, their use may be restricted because of the few number that can be recovered from adult tissues, their limited in vitro e...

Chronic inflammatory diseases are characterized by a bone destruction mediated by an increased osteoclast (OCL) activity. OCLs are phagocytic cells arising from the myeloid lineage. Indeed, OCLs derive from monocytes (MN-OCLs) and, in an inflammatory context, they also derive from dendritic cells (DC-OCLs). Despite this origin, their role in the immune responses is still unclear. OCLs in steady state have been reported to act as antigen-presenting cells that activate CD8+ regu...