Incretins and bone: friend or foe?

To adapt to its various functions, the bone tissue is remodeled permanently and is under the influence of hormonal, local, mechanical and nervous signals. Among them, a role for gut hormones in controlling bone mass and quality has emerged in the recent years. The aim of this review is to provide the reader with a summary of recent developments in the interaction between incretin hormones and bone physiology

Interplay between bone and incretin hormones: A review

Bone is a tissue with multiple functions that is built from the molecular to anatomical levels to resist and adapt to mechanical strains. Among all the factors that might control the bone organization, a role for several gut hormones called "incretins" has been suspected. The present review summarizes the current evidences on the effects of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) in bone physiology

Présentation des plateformes SCIAM et IRM-PRIMEX

Présentation des plateformes SCIAM et IRM-PRIMEX Guillaume Mabilleau et Florence Franconi Université d’Angers, Institut de Biologie en Santé, 49933 Angers, France Le service commun d’imageries et d’analyses microscopiques (SCIAM) et la plateforme d’Imagerie par Résonance Magnétique (IRM) préclinique – PRIMEX sont deux services communs de la SFR ICAT 4208 de l’Université d’Angers. Le SCIAM dispose d’un ensemble dispose d’un microtomographe à rayons X (Bruker microCT 1076) permettant l’acquisition in vivo à des résolutions de 9, 18 et 36 µm et d’un irradiateur à rayons X (Faxitron CP-160). La plateforme PRIMEX dispose d’un imageur Biospec 70/20 Avance III (Bruker Biospin) opérant à un champ magnétique de 7 Tesla. Ces équipements sont particulièrement adaptés pour l’imagerie de la souris ou du rat. Un tour d’horizon du potentiel de ces équipements en préclinique sera présenté. Ces équipements permettent des explorations in vivo chez le petit animal pour des applications telles que la caractérisation anatomique ou fonctionnelle de modèle animaux en oncologie, neurologie, cardiologie… ou l’évaluation de l’efficacité de nouveaux traitements thérapeutiques. Des applications dans d’autres domaines sont aussi possibles (végétal, agroalimentaire, matériaux, ex vivo…). Ces deux plateformes sont ouvertes aux partenaires institutionnels et industriels. Elles proposent un accompagnement scientifique et technique à la conception de projets ainsi que des formations dans le domaine de l’IRM préclinique

Number of Circulating CD14-Positive Cells and the Serum Levels of TNF-α Are Raised in Acute Charcot Foot

International audienc

Hypodynamia Alters Bone Quality and Trabecular Microarchitecture

Disuse induces a rapid bone loss in humans and animals; hypodynamia/sedentarity is now recognized as a risk factor for osteoporosis. Hypodynamia also decreases bone mass but its effects are largely unknown and only few animal models have been described. Hypodynamic chicken is recognized as a suitable model of bone loss but the effects on the quality have not been fully explored. We have used ten chickens bred in a large enclosure (FREE group); ten others were confined in small cages with little space to move around (HYPO group). They were sacrificed at 53 days and femurs were evaluated by microcomputed tomography (microCT) and nanoindentation. Sections (4 µm thick) were analyzed by Fourier Transform InfraRed Microspectroscopy (FTIR) to see the effects on mineralization and collagen and quantitative backscattered electron imaging (qBEI) to image the mineral of the bone matrix. Trabecular bone volume and microarchitecture were significantly altered in the HYPO group. FTIR showed a significant reduction of the mineral-to-matrix ratio in the HYPO group associated with an increase in the carbonate content and an increase in crystallinity (calculated as the area ratio of subbands located at 1020 and 1030 cm(-1)) indicating a poor quality of the mineral. Collagen maturity (calculated as the area ratio of subbands located at 1660 and 1690 cm(-1)) was significantly reduced in the HYPO group. Reduced biomechanical properties were observed at the tissue level. Confined chicken represents a new model for the study of hypodynamia because bone changes are not created by a surgical lesion or a traumatic method. Animals have a reduced bone mass and present with an altered bone matrix quality which is less mineralized and whose collagen contains less crosslinks than in control chicken

Aluminum and bone: Review of new clinical circumstances associated with Al(3+) deposition in the calcified matrix of bone

Several decades ago, aluminum encephalopathy associated with osteomalacia has been recognized as the major complication of chronic renal failure in dialyzed patients. Removal of aluminum from the dialysate has led to a disappearance of the disease. However, aluminum deposit occurs in the hydroxyapatite of the bone matrix in some clinical circumstances that are presented in this review. We have encountered aluminum in bone in patients with an increased intestinal permeability (coeliac disease), or in the case of prolonged administration of aluminum anti-acid drugs. A colocalisation of aluminum with iron was also noted in cases of hemochromatosis and sickle cell anemia. Aluminium was also identified in a series of patients with exostosis, a frequent benign bone tumor. Corrosion of prosthetic implants composed of grade V titanium (TA6V is an alloy containing 6% aluminum and 4% vanadium) was also observed in a series of hip or knee revisions. Aluminum can be identified in undecalcified bone matrix stained by solochrome azurine, a highly specific stain allowing the detection of 0.03 atomic %. Colocalization of aluminum and iron does not seem to be the fruit of chance but the cellular and molecular mechanisms are still poorly understood. Histochemistry is superior to spectroscopic analyses (EDS and WDS in scanning electron microscopy)

Polymerization of 2-(hydroxyethyl)methacrylate by two different initiator/accelerator systems: a Raman spectroscopic monitoring

The control of monomer polymerization is important when preparing biocompatible devices. The compound 2-(hydroxyethyl)methacrylate can be polymerized by redox systems using benzoyl peroxide (BPO) (as accelerator) and a substituted amine (as initiator). However, this system is associated with a highly exothermic polymerization, and end-products with inflammatory properties are produced. We have used ascorbic acid (AA) to induce BPO fragmentation and have compared the kinetics of the reaction, by Raman microscopy, with that obtained with a substituted amine. The breaking of the C= bond (Raman stretching vibration at 1641 cm−1) could be monitored in both cases and reflected the incorporation of new monomer molecules into the chain. The AA-induced polymerization was slower than with the substituted amine and was accompanied by the appearance of a new band at 1603 cm−1, assigned to the stretching vibrations of -COOH species incorporated into the chains. Raman microscopy appears to be a powerful tool in the study of polymeric biomaterial preparation

Incretin-based therapy for the treatment of bone fragility in diabetes mellitus

Bone fractures are common comorbidities of type 2 diabetes mellitus (T2DM). Bone fracture incidence seems to develop due to increased risk of falls, poor bone quality and/or anti-diabetic medications. Previously, a relation between gut hormones and bone has been suspected. Most recent evidences suggest indeed that two gut hormones, namely glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), may control bone remodeling and quality. The GIP receptor is expressed in bone cells and knockout of either GIP or its receptor induces severe bone quality alterations. Similar alterations are also encountered in GLP-1 receptor knock-out animals associated with abnormal osteoclast resorption. Some GLP-1 receptor agonist (GLP-1RA) have been approved for the treatment of type 2 diabetes mellitus and although clinical trials may not have been designed to investigate bone fracture, first results suggest that GLP-1RA may not exacerbate abnormal bone quality observed in T2DM. The recent design of double and triple gut hormone agonists may also represent a suitable alternative for restoring compromised bone quality observed in T2DM. However, although most of these new molecules demonstrated weight loss action, little is known on their bone safety. The present review summarizes the most recent findings on peptide-based incretin therapy and bone physiology

Glucose-dependent insulinotropic polypeptide (GIP) directly affects collagen fibril diameter and collagen cross-linking in osteoblast cultures.

Glucose-dependent insulinotropic polypeptide (GIP) is absolutely crucial in order to obtain optimal bone strength and collagen quality. However, as the GIPR is expressed in several tissues other than bone, it is difficult to ascertain whether the observed modifications of collagen maturity, reported in animal studies, were due to direct effects on osteoblasts or indirect through regulation of signals originating from other tissues. The aims of the present study were to investigate whether GIP can directly affect collagen biosynthesis and processing in osteoblast cultures and to decipher which molecular pathways were necessary for such effects. MC3T3-E1 cells were cultured in the presence of GIP ranged between 10 and 100pM. Collagen fibril diameter was investigated by electron microscopy whilst collagen maturity was determined by Fourier transform infra-red microspectroscopy (FTIRM). GIP treatment resulted in dose-dependent increases in lysyl oxidase activity and collagen maturity. Furthermore, GIP treatment shifted the collagen fiber diameter towards lower value but did not significantly affect collagen heterogeneity. GIP acted directly on osteoblasts by activating the adenylyl cyclase-cAMP pathway. This study provides evidences that GIP acts directly on osteoblasts and is capable of improving collagen maturity and fibril diameter

Metaplastic woven bone in bone metastases: A Fourier-transform infrared analysis and imaging of bone quality (FTIR)

Most osteolytic tumors are in fact mixed and contain an osteoblastic component associated with the predominant osteolytic areas. This metaplastic woven bone is always evidenced by histological analysis even in the absence of radiological expression. Metaplastic bone formation reflects the activation of new osteoblasts coming from the stimulation of the dormant lining cells. Twelve patients with secondary metastases of the iliac crest evidenced by hot spots on a Tc-MBP san were diagnosed by histomorphometry on bone biopsies. Fourier Transformed InfraRed analysis and Imaging (FTIRI) was used on 4μm thick sections of undecalcified bone. The mineralization degree, carbonate substitution, crystallinity and the cross-links ratio of collagen (1660/1690cm bands) were determined. The matrix characteristics were analyzed and imaged in the pre-existing residual bone and in the metaplastic woven bone in the vicinity of the tumor cells. FTIRI provided images of the phosphate, amide and combination of peak ratio after having selected the peaks of interest. In addition, the matrix properties can be measured and compared between the old and newly-formed bones. Woven bone appeared poorly calcified with a low phosphate/amide ratio (P=0.03) crystallinity (P<0.0001) and carbonate substitution (P=0.003). Collagen was less mature as evidenced by lower cross-links (P=0.01). Woven bone associated with bone metastasis appears poorly mineralized and rapidly elaborated by osteoblasts. The collagenous phase of the bone matrix has a low level of reticulation. FTIRI is a powerful tool to measure and visualize the various components of the bone matrix in human diseases