Exosomes Derived from Pg-LPS-activated Macrophages Promote Osteoclasts Differentiation via p38 MAPK/MMP-9 Signaling Pathway

doi:10.13701/j.cnki.kqyxyj.2026.07.005

Abstract

Abstract: Objective: To investigate whether exosomes derived from porphyromonas gingivalis-lipopolysaccharide (Pg-LPS)-activated macrophages promote osteoclasts differentiation via the p38 mitogen-activated protein kinase (p38 MAPK)/matrix metalloprotein 9 (MMP-9) signaling pathway. Methods: A mouse periodontitis model was established by ligature, and alveolar bone loss was assessed using micro-computed tomography (Micro-CT), quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot were used to detect CD11b, interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), MMP-9, and p38 MAPK expression. Macrophages were stimulated with Pg-LPS, conditioned medium (CM) and exosomes (exo) were collected and co-cultured with osteoclast precursor cells. MMP-9 and p38 MAPK expression and osteoclast differentiation tartrate-resistant acid phosphatase (TRAP staining) were evaluated. The role of p38 MAPK was further tested by injecting exosomes locally with/without the p38 inhibitor SB203580, and by adding SB203580 to co-cultured precursors. Results: Ligature-induced periodontitis increased bone loss and elevated inflammatory and targeted molecule expression. In vitro, LPS-CM/exo enhanced MMP-9 and p38 MAPK expression and osteoclastogenesis, however, the effects were inhibited by SB203580 (P<0.05). Conclusion: Exosomes derived from Pg-LPS-activated macrophages promote osteoclast differentiation via the p38 MAPK/MMP-9 signaling pathway, which drove periodontal bone loss.

Key words: Porphyromonas gingivalis-lipopolysaccharide, macrophage, osteoclast, exosome, p38 mitogen-activated protein kinase

CHENG Liting, XU Ruonan, QI Qi, XING Tian. Exosomes Derived from Pg-LPS-activated Macrophages Promote Osteoclasts Differentiation via p38 MAPK/MMP-9 Signaling Pathway[J]. Journal of Oral Science Research, 2026, 42(7): 575-583.

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