Recombinant Human Bone Morphogenetic Protein-2 Stimulates Osteoblastic Differentiation in Cells Isolated from Human Periodontal Ligament

Abstract

Periodontal ligament cells may play an important role in the successful regeneration of the periodontium. We investigated the effects of recombinant human bone morphogenetic protein-2 (rhBMP-2), one of the most potent growth factors that stimulates osteoblast differentiation and bone formation, on cell growth and osteoblastic differentiation in human periodontal ligament cells (HPLC) isolated from four adult patients. rhBMP-2 induced no significant changes in cell growth in any of the HPLCs. rhBMP-2 at concentrations over 50 ng/mL significantly stimulated alkaline phosphatase (ALPase) activity and parathyroid hormone (PTH)-dependent 3', 5'-cyclic adenosine monophosphate 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 factor-alpha inhibited the rhBMP-2-stimulated activity. Interleukin-6 induced no significant changes in ALPase activity stimulated with rhBMP-2. Although 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 D3 [1,25(OH)2D3] induced osteocalcin mRNA expression and protein synthesis in these cells. rhBMP-2 inhibited 1,25(OH)2D3-induced osteocalcin synthesis in HPLCs at both the mRNA and protein levels. These results suggest that rhBMP-2 provides an anabolic effect on periodontal regeneration by stimulation of osteoblastic differentiation in human periodontal ligament cells, and that this stimulatory effect is differentially modulated by inflammatory cytokines during the course of periodontal regeneration.

PLAP-1/Asporin, a Novel Negative Regulator of Periodontal Ligament Mineralization

“…BMP-2 has also been reported to stimulate osteoblastic differentiation of human PDL cells (20) and to promote dental follicle cells that are putative progenitor cells for the periodontium that differentiate into a cementoblastic/osteoblastic phenotype (21). As expected, BMP-2 enhanced the ALPase activity and the calcified nodule (9).…”

The role of heme oxygenase-1 in mechanical stress- and lipopolysaccharide-induced osteogenic differentiation in human periodontal ligament cells

“…4 The cells in the periodontal ligament are capable of differentiating into osteoblasts or cementoblasts in response to a mechanical stimulus. 5,6 The osteogenic differentiation of PDLCs is known to play a pivotal role in alveolar bone remodeling during orthodontic tooth movement. 4 In the bone microenvironment, bone morphogenetic proteins (BMP) play a critical role in the regulation of osteoblast differentiation and function.…”

Effect of Stretching Stress on Gene Transcription Related to Early-phase Differentiation in Rat Periodontal Ligament Cells

“…Some studies suggested that PE 2 and IL-1␤ induced by a cyclic stretching force mediated a decrease in ALP activity in PDL cells 12,17,21,23) . Other studies, however, have indicated that an increase in ALP activity is a sign of osteoblastic differentiation in PDL cells 7,13) . Our results showing that expression of ALP increased remarkably in both the 9% and 18% stretching groups suggest that application of a stretching load induces osteoblastic differentiation in PDL cells.…”

“…genesis [3][4][5][7][8][9][12][13][14][17][18][19][21][22][23][24][25] , that HSP70 was involved in homeostasis 1,16) , and that bFGF was closely involved in both functions 11,18,20) . Although the magnitude of human bite force varies, 500-3,000 g was selected as the standard force for clinical studies 2) .…”

“…BMPs, multifunctional growth factors belonging to the transforming growth factorbeta super-family, participate in the differentiation of undifferentiated mesenchymal cells to osteoblasts 14) . It has been reported that BMP-2 enhances expression of markers for osteoblastic differentiation such as ALP 4,7) , and also promotes osteoblastic differentiation of human PDL cells to decrease cell proliferation 8) . Increased expression of ALP mRNA in this study also suggests that cyclic stretching force affects PDL metabolism magnitudedependently.…”