HDL₃ reduces the association and modulates the metabolism of oxidized LDL by osteoblastic cells: A protection against cell death

Abstract

Oxidized low density lipoproteins (OxLDL) are known to promote atherosclerosis, but it is only recently that OxLDL have been associated with alterations of the functions of bone-forming osteoblasts and osteoporosis. Although high density lipoproteins (HDL) are recognized for their anti-atherogenic action, there is less information about their ability to protect against osteoporosis. Therefore, we investigated the capacity of HDL3 to prevent the cell death induced by OxLDL in human osteoblastic cells. Simultaneous exposure of the cells to HDL3 and OxLDL abolished the reduction of cell viability monitored by MTT activity measurement and the induction of apoptosis determined by annexin V staining indicating that HDL3 prevent the apoptosis of osteoblasts induced by OxLDL. This protection correlated with the displacement by HDL3 of OxLDL association to osteoblasts, signifying that OxLDL binding and/or internalization are/is necessary for their cytotoxic effects. We also found that exposition of osteoblastic cells to HDL3 prior to incubation with OxLDL reduced cell death and preserved the lysosomal integrity. This protection was correlated with an increase of SR-BI expression, a modification of OxLDL metabolism with less global uptake of OxLDL and greater selective uptake of cholesterol from OxLDL. These results strongly suggest that, as for atherosclerosis, HDL may exert beneficial actions on bone metabolism.

Scavenger receptor class B, type I (Scarb1) deficiency promotes osteoblastogenesis but stunts terminal osteocyte differentiation

“…), which agrees with our previous results in MG‐63 osteoblast‐like cells (Brodeur et al. ). However, neither the addition of HDL 3 nor LDL significantly modified proliferation in WT or null cells (Fig.…”

“…Since Scarb1-null mice display increased HDL levels, we therefore investigated the effects of HDL and the involvement of SR-BI in MSC proliferation. As shown in Figure 2A, Scarb1 expression was increased by incubation of WT MSC with HDL 3 , a subclass of HDL rich in apoA-I and binding more specifically to SR-BI (Rigotti et al 1997), which agrees with our previous results in MG-63 osteoblast-like cells (Brodeur et al 2008b). However, neither the addition of HDL 3 nor LDL significantly modified proliferation in WT or null cells (Fig.…”

Effect of hyperlipidemia on femoral biomechanics and morphology in low-density lipoprotein receptor gene knockout mice

“…The increase of HDL observed in WH animals was probably a determinant for the development of moderate hyperlipidemia in this group, whereas the L and LH groups presented low HDL levels and high levels of triglycerides, TC and its fractions, characterizing severe hyperlipidemia. In addition to its cardiovascular action, HDL inhibits osteoblast apoptosis induced by LDL, with beneficial effects on bone metabolism [23].…”

High density lipoprotein: it's not just about lipid transport anymore

“…Interaction of F1-ATPase with HDL not only protects against apoptotic signaling but also stimulates endothelial cell proliferation [56]. Different density fractions of HDL can have varying antiapoptotic capacities, with small dense HDL 3c having the most potent effects, shown on endothelial cells and osteoblasts [47,57]. Interestingly, this activity is impaired in patients with metabolic syndrome, possibly due to the changes in HDL particle protein and lipid composition seen in these patients [58].…”