Low-bone-mass phenotype of deficient mice for the cluster of differentiation 36 (CD36)

• Published in: PloS one 2013-10, Vol.8 (10), p.e77701-e77701
• Main Authors: Kevorkova, Olha, Martineau, Corine, Martin-Falstrault, Louise, Sanchez-Dardon, Jaime, Brissette, Louise, Moreau, Robert
• Format: Article
• Language: English
• Subjects: Animals; Biocompatibility; Biomedical materials; Blood Platelet Disorders - complications; Blood Platelet Disorders - genetics; Blood Platelet Disorders - metabolism; Blood Platelet Disorders - pathology; Bone and Bones - metabolism; Bone and Bones - pathology; Bone Density - genetics; Bone Density - physiology; Bone growth; Bone marrow; Bone mass; Bone resorption; Bone sialoprotein; Bone turnover; Cancellous bone; Cbfa-1 protein; CD36 antigen; CD36 Antigens - deficiency; CD36 Antigens - genetics; CD36 Antigens - metabolism; Cell culture; Cell Differentiation - genetics; Cell Differentiation - physiology; Cell Line; Cell survival; Computed tomography; Fatty acids; Femur; Femur - metabolism; Femur - pathology; Gene expression; Gene Expression - genetics; Genetic Diseases, Inborn - complications; Genetic Diseases, Inborn - genetics; Genetic Diseases, Inborn - metabolism; Genetic Diseases, Inborn - pathology; Histology; Lipids; Lipoproteins; Markers; Metabolism; Mice; Mice, Inbred C57BL; Mice, Knockout; Mineralization; Mouse devices; Osteoblasts; Osteoblasts - metabolism; Osteoblasts - pathology; Osteocalcin; Osteocalcin - blood; Osteocalcin - genetics; Osteocalcin - metabolism; Osteogenesis; Osteogenesis - genetics; Osteogenesis - physiology; Osteoporosis; Peptide Fragments - genetics; Peptide Fragments - metabolism; Phenotype; Physiology; Plasma levels; Procollagen; Procollagen - genetics; Procollagen - metabolism; Receptors; Scavenger receptors; Scavenger Receptors, Class B - genetics; Scavenger Receptors, Class B - metabolism; Spine; Stromal cells; Tibia - metabolism; Tibia - pathology; Vertebrae
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0077701

Bone tissue is continuously remodeled by bone cells and maintenance of its mass relies on the balance between the processes of resorption and formation. We have reported the expression of numerous scavenger receptors, namely scavenger receptor (SR) class B type I and II (SR-BI and SR-BII), and CD36, in bone-forming osteoblasts but their physiological roles in bone metabolism are still unknown. To unravel the role of CD36 in bone metabolism, we determined the bone phenotype of CD36 knockout (CD36KO) mice and characterized the cell functions of osteoblasts lacking CD36. Weights of CD36KO mice were significantly lower than corresponding wild-type (WT) mice, yet no significant difference was found in femoral nor tibial length between CD36KO and WT mice. Analysis of bone architecture by micro-computed tomography revealed a low bone mass phenotype in CD36KO mice of both genders. Femoral trabecular bone from 1 to 6 month-old CD36KO mice showed lower bone volume, higher trabecular separation and reduced trabeculae number compared to WT mice; similar alterations were noticed for lumbar vertebrae. Plasma levels of osteocalcin (OCN) and N-terminal propeptide of type I procollagen (PINP), two known markers of bone formation, were significantly lower in CD36KO mice than in WT mice, whereas plasma levels of bone resorption markers were similar. Accordingly, histology highlighted lower osteoblast perimeter and reduced bone formation rate. In vitro functional characterization of bone marrow stromal cells and osteoblasts isolated from CD36KO mice showed reduced cell culture expansion and survival, lower gene expression of osteoblastic Runt-related transcription factor 2 (Runx2) and osterix (Osx), as well as bone sialoprotein (BSP) and osteocalcin (OCN). Our results indicate that CD36 is mandatory for adequate bone metabolism, playing a role in osteoblast functions ensuring adequate bone formation.