M. Kobayashi et al., Recombinant human bone morphogenetic protein-2 stimulates osteoblastic differentiation in cells isolated from human periodontal ligament, J DENT RES, 78(10), 1999, pp. 1624-1633
Periodontal Ligament cells may play an important role in the successful reg
eneration of the periodontium. We investigated the effects of recombinant h
uman bone morphogenetic protein-2 (rhBMP-2), one of the most potent growth
factors that stimulates osteoblast differentiation and bone formation, on c
ell growth and osteoblastic differentiation in human periodontal ligament c
ells (HPLC) isolated from four adult patients. rhBMP-2 induced no significa
nt changes in cell growth in any of the HPLCs. rhBMP-2 at concentrations ov
er 50 ng/mL significantly stimulated alkaline phosphatase (ALPase) activity
and parathyroid hormone (PTH)-dependent 3', 5'-cyclic adenosine monophosph
ate accumulation, which are early markers of osteoblast differentiation, in
the HPLCs. rhBMP-2 (500 ng/mL) also slightly enhanced the level of PTH/PTH
-related peptide receptor mRNA expression in these cells. While interleukin
-1 beta enhanced ALPase activity stimulated with rhBMP-2, tumor necrosis fa
ctor-alpha inhibited the rhBMP-2-stimulated activity. Interleukin-6 induced
no significant changes in ALPase activity stimulated with rhBMP-2. Althoug
h HPLCs, whether treated with rhBMP-2 or not, could not produce measurable
amounts of osteocalcin, which is a marker of more mature osteoblasts, 1,25-
dihydroxyvitamin D-3[1,25(OH)(2)D-3] induced osteocalcin mRNA expression an
d protein synthesis in these cells. rhBMP-2 inhibited 1,25(OH)(2)D-3-induce
d osteocalcin synthesis in HPLCs at both the mRNA and protein levels. These
results suggest that rhBMP-2 provides an anabolic effect on periodontal re
generation by stimulation of osteoblastic differentiation in human periodon
tal ligament cells, and that this stimulatory effect is differentially modu
lated by inflammatory cytokines during the course of periodontal regenerati
on.