|
|
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result sql = Lenalidomide inhibits osteoclastogenesis, survival factors and bone-remodeling markers in multiple myeloma.
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result sql = Osteolytic bone disease in multiple myeloma (MM) is caused by enhanced osteoclast (OCL) activation and inhibition of osteoblast function. Lenalidomide and bortezomib have shown promising response rates in relapsed and newly diagnosed MM, and bortezomib has recently been reported to inhibit OCLs. We here investigated the effect of lenalidomide on OCL formation and osteoclastogenesis in comparison with bortezomib. Both drugs decreased alpha V beta 3-integrin, tartrate-resistant acid phosphatase-positive cells and bone resorption on dentin disks. In addition, both agents decreased receptor activator of nuclear factor-kappaB ligand (RANKL) secretion of bone marrow stromal cells (BMSCs) derived from MM patients. We identified PU.1 and pERK as major targets of lenalidomide, and nuclear factor of activated T cells of bortezomib, resulting in inhibition of osteoclastogenesis. Furthermore, downregulation of cathepsin K, essential for resorption of the bone collagen matrix, was observed. We demonstrated a significant decrease of growth and survival factors including macrophage inflammatory protein-alpha, B-cell activating factor and a proliferation-inducing ligand. Importantly, in serum from MM patients treated with lenalidomide, the essential bone-remodeling factor RANKL, as well as the RANKL/OPG ratio, were significantly reduced, whereas osteoprotegerin (OPG) was increased. We conclude that both agents specifically target key factors in osteoclastogenesis, and could directly affect the MM-OCL-BMSCs activation loop in osteolytic bone disease.
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result sql = Lenalidomide inhibits osteoclastogenesis, survival factors and bone-remodeling markers in multiple myeloma.
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char = s;code = 115
char = e;code = 101
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char = i;code = 105
char = n;code = 110
char = ;code = 32
char = m;code = 109
char = u;code = 117
char = l;code = 108
char = t;code = 116
char = i;code = 105
char = p;code = 112
char = l;code = 108
char = e;code = 101
char = ;code = 32
char = m;code = 109
char = y;code = 121
char = e;code = 101
char = l;code = 108
char = o;code = 111
char = m;code = 109
char = a;code = 97
char = ;code = 32
char = (;code = 40
char = M;code = 77
char = M;code = 77
char = );code = 41
char = ;code = 32
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = c;code = 99
char = a;code = 97
char = u;code = 117
char = s;code = 115
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = b;code = 98
char = y;code = 121
char = ;code = 32
char = e;code = 101
char = n;code = 110
char = h;code = 104
char = a;code = 97
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = o;code = 111
char = s;code = 115
char = t;code = 116
char = e;code = 101
char = o;code = 111
char = c;code = 99
char = l;code = 108
char = a;code = 97
char = s;code = 115
char = t;code = 116
char = ;code = 32
char = (;code = 40
char = O;code = 79
char = C;code = 67
char = L;code = 76
char = );code = 41
char = ;code = 32
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = h;code = 104
char = i;code = 105
char = b;code = 98
char = i;code = 105
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = o;code = 111
char = s;code = 115
char = t;code = 116
char = e;code = 101
char = o;code = 111
char = b;code = 98
char = l;code = 108
char = a;code = 97
char = s;code = 115
char = t;code = 116
char = ;code = 32
char = f;code = 102
char = u;code = 117
char = n;code = 110
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = .;code = 46
char = ;code = 32
char = L;code = 76
char = e;code = 101
char = n;code = 110
char = a;code = 97
char = l;code = 108
char = i;code = 105
char = d;code = 100
char = o;code = 111
char = m;code = 109
char = i;code = 105
char = d;code = 100
char = e;code = 101
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = b;code = 98
char = o;code = 111
char = r;code = 114
char = t;code = 116
char = e;code = 101
char = z;code = 122
char = o;code = 111
char = m;code = 109
char = i;code = 105
char = b;code = 98
char = ;code = 32
char = h;code = 104
char = a;code = 97
char = v;code = 118
char = e;code = 101
char = ;code = 32
char = s;code = 115
char = h;code = 104
char = o;code = 111
char = w;code = 119
char = n;code = 110
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = m;code = 109
char = i;code = 105
char = s;code = 115
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = p;code = 112
char = o;code = 111
char = n;code = 110
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = l;code = 108
char = a;code = 97
char = p;code = 112
char = s;code = 115
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = n;code = 110
char = e;code = 101
char = w;code = 119
char = l;code = 108
char = y;code = 121
char = ;code = 32
char = d;code = 100
char = i;code = 105
char = a;code = 97
char = g;code = 103
char = n;code = 110
char = o;code = 111
char = s;code = 115
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = M;code = 77
char = M;code = 77
char = ,;code = 44
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = b;code = 98
char = o;code = 111
char = r;code = 114
char = t;code = 116
char = e;code = 101
char = z;code = 122
char = o;code = 111
char = m;code = 109
char = i;code = 105
char = b;code = 98
char = ;code = 32
char = h;code = 104
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = c;code = 99
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = l;code = 108
char = y;code = 121
char = ;code = 32
char = b;code = 98
char = e;code = 101
char = e;code = 101
char = n;code = 110
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = p;code = 112
char = o;code = 111
char = r;code = 114
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = h;code = 104
char = i;code = 105
char = b;code = 98
char = i;code = 105
char = t;code = 116
char = ;code = 32
char = O;code = 79
char = C;code = 67
char = L;code = 76
char = s;code = 115
char = .;code = 46
char = ;code = 32
char = W;code = 87
char = e;code = 101
char = ;code = 32
char = h;code = 104
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = v;code = 118
char = e;code = 101
char = s;code = 115
char = t;code = 116
char = i;code = 105
char = g;code = 103
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = e;code = 101
char = f;code = 102
char = f;code = 102
char = e;code = 101
char = c;code = 99
char = t;code = 116
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = l;code = 108
char = e;code = 101
char = n;code = 110
char = a;code = 97
char = l;code = 108
char = i;code = 105
char = d;code = 100
char = o;code = 111
char = m;code = 109
char = i;code = 105
char = d;code = 100
char = e;code = 101
char = ;code = 32
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = O;code = 79
char = C;code = 67
char = L;code = 76
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = r;code = 114
char = m;code = 109
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = o;code = 111
char = s;code = 115
char = t;code = 116
char = e;code = 101
char = o;code = 111
char = c;code = 99
char = l;code = 108
char = a;code = 97
char = s;code = 115
char = t;code = 116
char = o;code = 111
char = g;code = 103
char = e;code = 101
char = n;code = 110
char = e;code = 101
char = s;code = 115
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = m;code = 109
char = p;code = 112
char = a;code = 97
char = r;code = 114
char = i;code = 105
char = s;code = 115
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = b;code = 98
char = o;code = 111
char = r;code = 114
char = t;code = 116
char = e;code = 101
char = z;code = 122
char = o;code = 111
char = m;code = 109
char = i;code = 105
char = b;code = 98
char = .;code = 46
char = ;code = 32
char = B;code = 66
char = o;code = 111
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = d;code = 100
char = r;code = 114
char = u;code = 117
char = g;code = 103
char = s;code = 115
char = ;code = 32
char = d;code = 100
char = e;code = 101
char = c;code = 99
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = a;code = 97
char = l;code = 108
char = p;code = 112
char = h;code = 104
char = a;code = 97
char = ;code = 32
char = V;code = 86
char = ;code = 32
char = b;code = 98
char = e;code = 101
char = t;code = 116
char = a;code = 97
char = ;code = 32
char = 3;code = 51
char = -;code = 45
char = i;code = 105
char = n;code = 110
char = t;code = 116
char = e;code = 101
char = g;code = 103
char = r;code = 114
char = i;code = 105
char = n;code = 110
char = ,;code = 44
char = ;code = 32
char = t;code = 116
char = a;code = 97
char = r;code = 114
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = -;code = 45
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = i;code = 105
char = s;code = 115
char = t;code = 116
char = a;code = 97
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = a;code = 97
char = c;code = 99
char = i;code = 105
char = d;code = 100
char = ;code = 32
char = p;code = 112
char = h;code = 104
char = o;code = 111
char = s;code = 115
char = p;code = 112
char = h;code = 104
char = a;code = 97
char = t;code = 116
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = -;code = 45
char = p;code = 112
char = o;code = 111
char = s;code = 115
char = i;code = 105
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = e;code = 101
char = ;code = 32
char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = b;code = 98
char = o;code = 111
char = n;code = 110
char = e;code = 101
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = o;code = 111
char = r;code = 114
char = p;code = 112
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = d;code = 100
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = d;code = 100
char = i;code = 105
char = s;code = 115
char = k;code = 107
char = s;code = 115
char = .;code = 46
char = ;code = 32
char = I;code = 73
char = n;code = 110
char = ;code = 32
char = a;code = 97
char = d;code = 100
char = d;code = 100
char = i;code = 105
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ,;code = 44
char = ;code = 32
char = b;code = 98
char = o;code = 111
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = a;code = 97
char = g;code = 103
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = s;code = 115
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char = d;code = 100
char = e;code = 101
char = c;code = 99
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = c;code = 99
char = e;code = 101
char = p;code = 112
char = t;code = 116
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = a;code = 97
char = t;code = 116
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = n;code = 110
char = u;code = 117
char = c;code = 99
char = l;code = 108
char = e;code = 101
char = a;code = 97
char = r;code = 114
char = ;code = 32
char = f;code = 102
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = o;code = 111
char = r;code = 114
char = -;code = 45
char = k;code = 107
char = a;code = 97
char = p;code = 112
char = p;code = 112
char = a;code = 97
char = B;code = 66
char = ;code = 32
char = l;code = 108
char = i;code = 105
char = g;code = 103
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = (;code = 40
char = R;code = 82
char = A;code = 65
char = N;code = 78
char = K;code = 75
char = L;code = 76
char = );code = 41
char = ;code = 32
char = s;code = 115
char = e;code = 101
char = c;code = 99
char = r;code = 114
char = e;code = 101
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = b;code = 98
char = o;code = 111
char = n;code = 110
char = e;code = 101
char = ;code = 32
char = m;code = 109
char = a;code = 97
char = r;code = 114
char = r;code = 114
char = o;code = 111
char = w;code = 119
char = ;code = 32
char = s;code = 115
char = t;code = 116
char = r;code = 114
char = o;code = 111
char = m;code = 109
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = s;code = 115
char = ;code = 32
char = (;code = 40
char = B;code = 66
char = M;code = 77
char = S;code = 83
char = C;code = 67
char = s;code = 115
char = );code = 41
char = ;code = 32
char = d;code = 100
char = e;code = 101
char = r;code = 114
char = i;code = 105
char = v;code = 118
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = f;code = 102
char = r;code = 114
char = o;code = 111
char = m;code = 109
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char = M;code = 77
char = M;code = 77
char = ;code = 32
char = p;code = 112
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = s;code = 115
char = .;code = 46
char = ;code = 32
char = W;code = 87
char = e;code = 101
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char = i;code = 105
char = d;code = 100
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = i;code = 105
char = f;code = 102
char = i;code = 105
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = P;code = 80
char = U;code = 85
char = .;code = 46
char = 1;code = 49
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = p;code = 112
char = E;code = 69
char = R;code = 82
char = K;code = 75
char = ;code = 32
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = m;code = 109
char = a;code = 97
char = j;code = 106
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = t;code = 116
char = a;code = 97
char = r;code = 114
char = g;code = 103
char = e;code = 101
char = t;code = 116
char = s;code = 115
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = l;code = 108
char = e;code = 101
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char = a;code = 97
char = l;code = 108
char = i;code = 105
char = d;code = 100
char = o;code = 111
char = m;code = 109
char = i;code = 105
char = d;code = 100
char = e;code = 101
char = ,;code = 44
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = n;code = 110
char = u;code = 117
char = c;code = 99
char = l;code = 108
char = e;code = 101
char = a;code = 97
char = r;code = 114
char = ;code = 32
char = f;code = 102
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = a;code = 97
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char = e;code = 101
char = d;code = 100
char = ;code = 32
char = T;code = 84
char = ;code = 32
char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = s;code = 115
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = b;code = 98
char = o;code = 111
char = r;code = 114
char = t;code = 116
char = e;code = 101
char = z;code = 122
char = o;code = 111
char = m;code = 109
char = i;code = 105
char = b;code = 98
char = ,;code = 44
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = u;code = 117
char = l;code = 108
char = t;code = 116
char = i;code = 105
char = n;code = 110
char = g;code = 103
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char = i;code = 105
char = n;code = 110
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char = i;code = 105
char = n;code = 110
char = h;code = 104
char = i;code = 105
char = b;code = 98
char = i;code = 105
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = o;code = 111
char = s;code = 115
char = t;code = 116
char = e;code = 101
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char = c;code = 99
char = l;code = 108
char = a;code = 97
char = s;code = 115
char = t;code = 116
char = o;code = 111
char = g;code = 103
char = e;code = 101
char = n;code = 110
char = e;code = 101
char = s;code = 115
char = i;code = 105
char = s;code = 115
char = .;code = 46
char = ;code = 32
char = F;code = 70
char = u;code = 117
char = r;code = 114
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = r;code = 114
char = m;code = 109
char = o;code = 111
char = r;code = 114
char = e;code = 101
char = ,;code = 44
char = ;code = 32
char = d;code = 100
char = o;code = 111
char = w;code = 119
char = n;code = 110
char = r;code = 114
char = e;code = 101
char = g;code = 103
char = u;code = 117
char = l;code = 108
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = c;code = 99
char = a;code = 97
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = p;code = 112
char = s;code = 115
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = K;code = 75
char = ,;code = 44
char = ;code = 32
char = e;code = 101
char = s;code = 115
char = s;code = 115
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = i;code = 105
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = s;code = 115
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result sql = Osteolytic bone disease in multiple myeloma (MM) is caused by enhanced osteoclast (OCL) activation and inhibition of osteoblast function. Lenalidomide and bortezomib have shown promising response rates in relapsed and newly diagnosed MM, and bortezomib has recently been reported to inhibit OCLs. We here investigated the effect of lenalidomide on OCL formation and osteoclastogenesis in comparison with bortezomib. Both drugs decreased alpha V beta 3-integrin, tartrate-resistant acid phosphatase-positive cells and bone resorption on dentin disks. In addition, both agents decreased receptor activator of nuclear factor-kappaB ligand (RANKL) secretion of bone marrow stromal cells (BMSCs) derived from MM patients. We identified PU.1 and pERK as major targets of lenalidomide, and nuclear factor of activated T cells of bortezomib, resulting in inhibition of osteoclastogenesis. Furthermore, downregulation of cathepsin K, essential for resorption of the bone collagen matrix, was observed. We demonstrated a significant decrease of growth and survival factors including macrophage inflammatory protein-alpha, B-cell activating factor and a proliferation-inducing ligand. Importantly, in serum from MM patients treated with lenalidomide, the essential bone-remodeling factor RANKL, as well as the RANKL/OPG ratio, were significantly reduced, whereas osteoprotegerin (OPG) was increased. We conclude that both agents specifically target key factors in osteoclastogenesis, and could directly affect the MM-OCL-BMSCs activation loop in osteolytic bone disease.
Publication: Leukemia 2008 Oct ;22(10)::1925-32. :doi: 10.1038/leu.2008.174.
Publication Date: 2008 Oct
Study Author(s): Breitkreutz, I;Raab, M S;Vallet, S;Hideshima, T;Raje, N;Mitsiades, C;Chauhan, D;Okawa, Y;Munshi, N C;Richardson, P G;Anderson, K C;
Institution: Department of Medical Oncology, LeBow Institute for Myeloma Therapeutics, Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA. [email protected]
Shortcut link to this study:
Publication Date: 2008 Oct
Study Author(s): Breitkreutz, I;Raab, M S;Vallet, S;Hideshima, T;Raje, N;Mitsiades, C;Chauhan, D;Okawa, Y;Munshi, N C;Richardson, P G;Anderson, K C;
Institution: Department of Medical Oncology, LeBow Institute for Myeloma Therapeutics, Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA. [email protected]
Shortcut link to this study:
Osteolytic bone disease in multiple myeloma (MM) is caused by enhanced osteoclast (OCL) activation and inhibition of osteoblast function. Lenalidomide and bortezomib have shown promising response rates in relapsed and newly diagnosed MM, and bortezomib has recently been reported to inhibit OCLs. We here investigated the effect of lenalidomide on OCL formation and osteoclastogenesis in comparison with bortezomib. Both drugs decreased alpha V beta 3-integrin, tartrate-resistant acid phosphatase-positive cells and bone resorption on dentin disks. In addition, both agents decreased receptor activator of nuclear factor-kappaB ligand (RANKL) secretion of bone marrow stromal cells (BMSCs) derived from MM patients. We identified PU.1 and pERK as major targets of lenalidomide, and nuclear factor of activated T cells of bortezomib, resulting in inhibition of osteoclastogenesis. Furthermore, downregulation of cathepsin K, essential for resorption of the bone collagen matrix, was observed. We demonstrated a significant decrease of growth and survival factors including macrophage inflammatory protein-alpha, B-cell activating factor and a proliferation-inducing ligand. Importantly, in serum from MM patients treated with lenalidomide, the essential bone-remodeling factor RANKL, as well as the RANKL/OPG ratio, were significantly reduced, whereas osteoprotegerin (OPG) was increased. We conclude that both agents specifically target key factors in osteoclastogenesis, and could directly affect the MM-OCL-BMSCs activation loop in osteolytic bone disease.
PMID: 18596740
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