Deciphering Cell-specific Effect of Osteoblast-Macrophage Crosstalk in Periodontitis Article (Faculty180)

cited authors

  • Jacho, Diego; Babaniamansour, Parto; Osorio, Raquel; Toledano, Manuel; Rabino, Agustin; Garcia-Mata, Rafael; Yildirim-Ayan, Eda


  • In periodontitis, the bone remodeling process is disrupted by the prevalent involvement of bacteria-induced pro-inflammatory macrophage cells and their interaction between osteoblast cells residing within the infected bone tissue. The complex interaction between the cells needs to be deciphered to understand the dominant player in tipping the balance from osteogenesis to osteoclastogenesis. Yet, only a few studies have looked at the crosstalk interaction between osteoblasts and macrophages using biomimetic three-dimensional (3D) tissue-like matrices. In this study, we created a cell-laden 3D tissue analog to study indirect crosstalk between these two cell types and the direct synergistic effect when they were cultured together on a 3D scaffold. The cell-specific role on osteoclast differentiation was investigated through osteoblast- and pro-inflammatory macrophage-specific feedback studies. The results suggested that when macrophages were exposed to osteoblasts-derived conditioned media from the mineralized matrix, the M1 macrophages tended to maintain their pro-inflammatory phenotype. Further, when osteoblasts were exposed to secretions from pro-inflammatory macrophages, they demonstrated elevated Receptor activator of NF-kB ligand (RANKL) expression and decreased ALP activities compared to osteoblasts exposed to only osteogenic media. In addition, the upregulation of TNF-α and c-Fos in pro-inflammatory macrophages within the 3D matrix indirectly increased the RANKL expression and reduced the ALP activity of osteoblasts, which in turn promoted osteoclastogenesis. The contact co-culturing with osteoblast and pro-inflammatory macrophages within 3D matrix demonstrated that the pro-inflammatory markers (TNFα and IL1β) expressions were upregulated. In contrast, anti-inflammatory marker (CCL18) were downregulated and osteoclastic markers (TRAP 6 and ACP5) were unchanged. The data suggested that the osteoblasts curbed the osteoclastic differentiation of macrophages while macrophages still preserve their pro-inflammatory lineages. The osteoblast within the 3D co-culture demonstrated increased ALP activity and did not express RANKL significantly different than the osteoblast cultured within a 3D collagen matrix without macrophages. Contact co-culturing has an anabolic effect on bone tissue in a bacteria-derived inflammatory environment.

publication date

  • 2023

published in