ArticleBone reports2026
Osteogenic differentiation of gingival and periodontal ligament fibroblasts inhibits osteoclast formation in 2D and 3D fibrin cultures.
Article in Bone reports, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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8 authors.
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Abstract
Bone regeneration requires coordinated interactions between multiple cell types responding to biochemical and biomechanical cues from the extracellular matrix (ECM). Gingival fibroblasts (GFs) and periodontal ligament fibroblasts (PDLFs) contribute to the regeneration of lost alveolar bone, as they can differentiate into osteoblast-like cells and regulate osteoclastogenesis. However, it remains unclear whether these two fibroblast populations contribute similarly to bone regeneration and how ECM properties modulate their osteogenic differentiation and subsequent osteoclast-inducing capacity. Here, we compared the osteogenic potential of GFs and PDLFs from 12 donors, cultured in 2D monolayers or 3D fibrin hydrogels under normal or osteogenic conditions, and assessed how fibroblast-conditioned media regulates osteoclast formation from peripheral blood mononuclear cells (PBMCs). Both fibroblast populations underwent osteogenic differentiation, as evidenced by increased alkaline phosphatase (ALP) activity, calcium deposition, and robust mineral nodule formation in 3D fibrin hydrogels. Osteogenic stimulation reduced macrophage colony-stimulating factor (M-CSF) secretion and increased osteoprotegerin (OPG) release. Functionally, conditioned media from non-osteogenic cultures promoted formation of multinucleated TRAcP-positive osteoclasts and upregulated osteoclast-associated genes, including TRACP, RANK, Cathepsin K, and the fusion marker DC-STAMP. In contrast, osteogenic differentiation attenuated the osteoclast-inducing capacity of both fibroblast populations. Across all parameters, GFs and PDLFs displayed largely comparable osteogenic and osteoclast-modulating phenotypes, irrespective of culture dimensionality. These findings indicate that osteogenic differentiation functions as a regulatory switch that diminishes the osteoclast-inductive potential of oral fibroblasts and support the interchangeable use of GFs and PDLFs in periodontal regenerative strategies.
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