K. Kawasaki et al., EFFECTS OF RECOMBINANT HUMAN BONE MORPHOGENETIC PROTEIN-2 ON DIFFERENTIATION OF CELLS ISOLATED FROM HUMAN BONE, MUSCLE, AND SKIN, Bone (New York, N.Y.), 23(3), 1998, pp. 223-231
We investigated the effects of recombinant human BMP-2 (rhBMP-2) on di
fferentiation of cells isolated from human bone, muscle, and skin. Cel
ls isolated from bones of sis patients (HBM-1 to HBM-6), muscle from f
ive patients (HM-1 to HM-5), and skin from three patients (HF-1 to HF-
3) were used, rhBMP-2 had no effects on proliferation of two HBM cells
, but had a stimulatory effect on three HM cell samples, rhBMP-2 stimu
lated both alkaline phosphatase (ALP) activity in all HBM cells and pa
rathyroid hormone (PTH)-dependent cAMP production in three of the four
HBM cell samples, although the magnitudes of these stimulatory effect
s differed among the cells tested. Although none of the HBM cells exam
ined produced detectable amounts of osteocalcin in the absence of 1,25
-(OH)(2)vitamin D-3, they synthesized measurable amounts of osteocalci
n in its presence. rhBMP-2 inhibited 1,25-(OH)(2)vitamin D-3-dependent
osteocalcin production in all of the HBM cell samples. Transplantatio
n of HBM-6 cells with rhBMP-2 using diffusion chambers into the perito
neal cavity of athymic mice induced formation of cartilage and bone in
the diffusion chambers, but neither cartilage nor bone was formed in
chambers transplanted without rhBMP-2, rhBMP-2 also stimulated ALP act
ivity in all of the HM and HF cell samples examined and PTH-dependent
cAMP production in three of four HM cell samples. rhBMP-2 induced no o
steocalcin production in any of the HM or HF cells in the presence of
1,25-(OH)(2)vitamin D-3. rhBMP-2 markedly inhibited myotube formation
by all of the HM cell samples. Transplantation of HM-4 cells with rhBM
P-2, using diffusion chambers, into athymic mice induced ALP-positive
cells in the chambers, but neither cartilage nor bone was observed. Th
ese results suggest that rhBMP-2, is a potent stimulator of osteoblast
differentiation and bone formation in human cells. (Bone 23: 223-231;
1998) (C) 1998 by Elsevier Science Inc. All rights reserved.