Direct cell–cell contact between periodontal ligament fibroblasts and osteoclast precursors synergistically increases the expression of genes related to osteoclastogenesis

Abstract

The formation of bone resorbing osteoclasts in vivo is orchestrated by cells of the osteoblast lineage such as periodontal ligament fibroblasts that provide the proper signals to osteoclast precursors. Although the requirement of cell-cell interactions is widely acknowledged, it is unknown whether these interactions influence the expression of genes required for osteoclastogenesis and the ultimate formation of osteoclasts. In the present study we investigated the effect of cell-cell interaction on the mRNA expression of adhesion molecules and molecules involved in osteoclast formation in cultures of peripheral blood mononuclear cells (PBMCs) and human primary periodontal ligament fibroblasts, both as solitary cultures and in co-culture. We further analyzed the formation of multinucleated, tartrate resistant acid phosphatase (TRACP) positive cells and assessed their bone resorbing abilities. Interestingly, gene expression of intercellular adhesion molecule-1 (ICAM-1) and of osteoclastogenesis-related genes (RANKL, RANK, TNF-alpha, and IL-1beta) was highly up-regulated in the co-cultures compared to mono-cultures and the 5-10-fold up-regulation reflected a synergistic increase due to direct cell-cell interaction. This induction strongly overpowered the effects of known osteoclastogenesis inducers 1,25(OH)(2)VitD(3) and dexamethasone. In case of indirect cell-cell contact mRNA expression was not altered, indicating that heterotypic adhesion is required for the increase in gene expression. In addition, the number of osteoclast-like cells that were formed in co-culture with periodontal ligament fibroblasts was significantly augmented compared to mono-cultures. Our data indicate that cell-cell adhesion between osteoclast precursors and periodontal ligament fibroblasts significantly modulates the cellular response which favors the expression of osteoclast differentiation genes and the ultimate formation of osteoclasts.

Osteogenic differentiation of human ligament fibroblasts induced by conditioned medium of osteoclast-like cells

“…No previous reports have described the effects of osteoclasts on fibroblasts, but studies have found that fibroblasts can induce differentiation of precursor cells into mature osteoclasts. Bloemen and colleagues (9) found that gene expression of intercellular adhesion molecule-1 (ICAM-1) and osteoclastogenesis-related genes (RANKL, RANK, TNF-a, and IL-1b) was highly up-regulated in co-cultures with fibroblasts. The current study has shown that conditioned medium of osteoclastlike cells can influence the adhesion molecule pathway of fibroblasts.…”

Glucocorticoids: Dose-related effects on osteoclast formation and function via reactive oxygen species and autophagy

“…It is well known that bone homeostasis is a dynamic balance that is maintained by bone formation and bone resorption [1,2]. Osteoclasts, which develop from hematopoietic osteoclast precursors, are the principle cells responsible for bone resorption [3].…”

Sex-specific effects of estrogen and androgen on gene expression in human monocyte-derived osteoclasts

“…In RAW 264.7 osteoclastic cells, PTEN overexpression antagonizes RANKL-stimulated osteoclast survival and osteopontin-stimulated cell migration [Sugatani et al, 2003]. ICAM1, which encodes a glycoprotein that binds to several integrin classes, is important in osteoclastogenesis [Kurachi et al, 1993;Okada et al, 2002;Garcia-Palacios et al, 2007;Bloemen et al, 2010]. Thus, the currently observed stimulatory effect of testosterone on ICAM1 is paradoxical, and merits further investigation as to its physiological or pathophysiological significance.…”