TY - JOUR
T1 - Increased osteoclast formation and activity by peripheral blood mononuclear cells in chronic liver disease patients with osteopenia
AU - Olivier, B.J.
AU - Schoenmaker, A.M.
AU - Mebius, R.E.
AU - Everts, V.
AU - Mulder, C.J.
AU - van Nieuwkerk, K.M.J.
AU - de Vries, T.J.
AU - van der Merwe, S.W.
AU - Schoenmaker, T.
AU - van Nieuwkerk, C.M.J.
PY - 2008
Y1 - 2008
N2 - Osteoporosis is a common complication of chronic liver disease, and the underlying mechanisms are not understood. We aimed to determine if osteoclasts develop from osteoclast precursors in peripheral blood mononuclear cells (PBMCs) of chronic liver disease patients with osteopenia compared with controls. PBMCs were isolated and fluorescence-activated cell sorting was performed to quantify the activated T lymphocyte population and receptor activator of nuclear factor kappa beta ligand (RANKL) expression. The activated T lymphocyte populations were comparable for all 3 groups, and RANKL was not detectable. The percentage of CD14+CD11b+ cells containing osteoclast precursors was comparable between the 3 groups. To assess the formation and functional activity of osteoclasts formed from circulating mononuclear cells, PBMCs were cultured (1) without addition of cytokines, (2) with macrophage colony stimulating factor (M-CSF), (3) with M-CSF and osteoprotegerin, and (4) with M-CSF and RANKL. The number of tartrate-resistant acid phosphatase-positive multinucleated cells and bone resorption was assessed. PBMCs from chronic liver disease patients with ostcopenia formed more osteoclast-like cells, which, when cultured in the presence of M-CSF and RANKL resorbed more bone than controls. The number of osteoclast-like cells and the amount of bone resorption correlated with lumbar bone densities. Addition of M-CSF increased numbers of osteoclast-like cells formed in healthy controls; however, this was not observed in either of the chronic liver disease groups. Plasma levels of M-CSF were elevated in both patient groups compared with healthy controls. Conclusion: Circulating mononuclear cells from chronic liver disease patients with osteopenia have a higher capacity to become osteoclasts than healthy controls or chronic liver disease patients without osteopenia. This could partially be due to priming with higher levels of M-CSF in the circulation.
AB - Osteoporosis is a common complication of chronic liver disease, and the underlying mechanisms are not understood. We aimed to determine if osteoclasts develop from osteoclast precursors in peripheral blood mononuclear cells (PBMCs) of chronic liver disease patients with osteopenia compared with controls. PBMCs were isolated and fluorescence-activated cell sorting was performed to quantify the activated T lymphocyte population and receptor activator of nuclear factor kappa beta ligand (RANKL) expression. The activated T lymphocyte populations were comparable for all 3 groups, and RANKL was not detectable. The percentage of CD14+CD11b+ cells containing osteoclast precursors was comparable between the 3 groups. To assess the formation and functional activity of osteoclasts formed from circulating mononuclear cells, PBMCs were cultured (1) without addition of cytokines, (2) with macrophage colony stimulating factor (M-CSF), (3) with M-CSF and osteoprotegerin, and (4) with M-CSF and RANKL. The number of tartrate-resistant acid phosphatase-positive multinucleated cells and bone resorption was assessed. PBMCs from chronic liver disease patients with ostcopenia formed more osteoclast-like cells, which, when cultured in the presence of M-CSF and RANKL resorbed more bone than controls. The number of osteoclast-like cells and the amount of bone resorption correlated with lumbar bone densities. Addition of M-CSF increased numbers of osteoclast-like cells formed in healthy controls; however, this was not observed in either of the chronic liver disease groups. Plasma levels of M-CSF were elevated in both patient groups compared with healthy controls. Conclusion: Circulating mononuclear cells from chronic liver disease patients with osteopenia have a higher capacity to become osteoclasts than healthy controls or chronic liver disease patients without osteopenia. This could partially be due to priming with higher levels of M-CSF in the circulation.
U2 - https://doi.org/10.1002/hep.21971
DO - https://doi.org/10.1002/hep.21971
M3 - Article
C2 - 18022900
SN - 0270-9139
VL - 47
SP - 259
EP - 267
JO - Hepatology
JF - Hepatology
IS - 1
ER -