Introduction: Recent data suggest that lipid metabolism imbalances affect osteoblast and osteoclast function resulting in altered bone mass quality and quantity. Here we investigated the role of apolipoprotein A-I (apoA-I), key-element in HDL biogenesis in the pathogenesis of osteoporosis in mice.
Materials and methods: Lumbar vertebrae and femora from apoA-I deficient (ApoA-I−/−) and WT (ApoA-I+/+, WT) mice were used for histological, histomorphometrical, spectrometric and in vitro analyses. Osteoclast precursors and bone marrow mesenchymal stem cells (BMMSCs) were isolated, cultured and differentiated towards osteoclasts and osteoblasts, respectively. BMMSC were assessed for PPARγ and Runx2 expression, using western blotting, flow cytometry and qRT-PCR. Differentiated osteoblasts were stained with von Kossa and ALP and examined for Runx2, osteopontin, osteocalcin, RankL, osteoprotegerin and Col1a1 expression. Differentiated osteoclasts were subjected to TRAP staining and qRT-PCR for Rank, Trap and cathepsin-K mRNA expression.
Results: MicroCT analysis revealed significantly reduced bone mass and Raman spectometry remarkably reduced collagen cross-linking in the ApoA-I−/− compared to the WT mice. Dynamic histomorphometry uncovered decreased osteoblast surface, bone formation and mineral apposition rate in ApoA-I−/− mice. Notably, no changes were observed in osteoclast resorption areas. BMMSCs from ApoA-I−/− mice displayed significantly decreased Runx2 but augmented PPARγ expression. Von Kossa and ALP stains were less extensive in the ApoA-I−/− compared to WT mice osteoblasts. RankL and osteoprotegerin mRNA levels were similar in the two groups, while Col1a1, osteopontin and osteocalcin mRNA expression were decreased in ApoA-I−/− mice. In accordance with TRAP staining, Rank, Trap and cathepsin-K mRNA levels showed no significant differences between osteoclasts from the two experimental groups.
Conclusions: Our findings provide novel evidence that ApoA-I deficiency diversely affects osteoblastogenesis and lipoblastogenesis resulting in impaired bone synthesis/quality, while osteoclast function remains unaffected. We hypothesize that perturbation in HDL metabolism might be implicated in the pathobiology of osteoporosis in mice.
17 - 20 May 2014
European Calcified Tissue Society