Liraglutide regulate osteogenesis-resorption via macrophage under compressive stress
- 1Stomatological Hospital of Dalian University (Dalian Stomatological Hospital)
- 2School of Stomatology, Dalian Medical University
- 3Affiliated Zhongshan Hospital of Dalian University
Abstract
Objectives: Joint diseases always caused by mechanical pressure induced-inflammation and bone resorption. With advancing age, joint wear-and-tear intensifies while reparative capacity diminishes. Liraglutide is a common medication used to lower blood sugar and improve blood lipids, and it is widely used in elderly patients. This study investigated whether liraglutide (Lira) regulates macrophage-mediated bone metabolism under mechanical pressure and elucidated the molecular mechanisms.
Methods: RAW264.7 macrophages were exposed to varying pressures (1–3 g/cm ² ) via custom-weighted glass coverslips. Cell viability was assessed by CCK-8 and Live/Dead staining. Cells were pretreated with 250 nmol/L Lira, and the expression of osteoclast-related (Piezo1, NFATc1, TRAP) and inflammation-related (TNF-α, iNOS, IL-1β, TRAF6, NF-κB/p-NF-κB) molecules was detected by qRT-PCR, immunofluorescence, and Western blotting. Conditioned media from treated macrophages were used to culture MC3T3-E1 pre-osteoblasts, and osteogenic markers (BMP2, RUNX2, ALP, OCN) were evaluated.
Results: Pressure at 2 g/cm ² for 4 h optimally induced osteoclastogenesis and inflammation. Lira did not affect Piezo1 expression but significantly suppressed NFATc1 and TRAP at both mRNA and protein levels. Lira also inhibited the TRAF6-NF-κB pathway, reducing TNF-α, iNOS, and IL-1β expression. Conditioned media from Lira-treated macrophages significantly upregulated BMP2, RUNX2, ALP, and OCN in MC3T3-E1 cells, indicating indirect promotion of osteogenesis.
Conclusion: Liraglutide reverses pressure-induced bone metabolic imbalance through a triple mechanism: inhibiting osteoclastogenesis, attenuating inflammation, and indirectly promoting osteogenesis via macrophage modulation. This study provides the first evidence of liraglutide’s molecular network in regulating bone metabolism under mechanical stress, supporting its therapeutic potential in pressure-related degenerative joint diseases such as osteoarthritis and temporomandibular joint osteoarthritis.
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BibTeX
@article{kong2026liraglutide,
title = {{Liraglutide regulate osteogenesis-resorption via macrophage under compressive stress}},
author = {Runze Kong and Difei Wu and Xiaochen Men and Yuzhu He and Qitao Du and Shuang Liu},
journal = {Frontiers in Pharmacology},
year = {2026},
month = oct,
doi = {10.3389/fphar.2026.1985291},
url = {https://www.frontiersin.org/articles/10.3389/fphar.2026.1985291/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Liraglutide regulate osteogenesis-resorption via macrophage under compressive stress
AU - Runze Kong
AU - Difei Wu
AU - Xiaochen Men
AU - Yuzhu He
AU - Qitao Du
AU - Shuang Liu
PY - 2026
DA - 2026/10/26
JO - Frontiers in Pharmacology
DO - 10.3389/fphar.2026.1985291
UR - https://www.frontiersin.org/articles/10.3389/fphar.2026.1985291/full
AB - Objectives: Joint diseases always caused by mechanical pressure induced-inflammation and bone resorption. With advancing age, joint wear-and-tear intensifies while reparative capacity diminishes. Liraglutide is a common medication used to lower blood sugar and improve blood lipids, and it is widely used in elderly patients. This study investigated whether liraglutide (Lira) regulates macrophage-mediated bone metabolism under mechanical pressure and elucidated the molecular mechanisms. Methods: RAW264.7 macrophages were exposed to varying pressures (1–3 g/cm ² ) via custom-weighted glass coverslips. Cell viability was assessed by CCK-8 and Live/Dead staining. Cells were pretreated with 250 nmol/L Lira, and the expression of osteoclast-related (Piezo1, NFATc1, TRAP) and inflammation-related (TNF-α, iNOS, IL-1β, TRAF6, NF-κB/p-NF-κB) molecules was detected by qRT-PCR, immunofluorescence, and Western blotting. Conditioned media from treated macrophages were used to culture MC3T3-E1 pre-osteoblasts, and osteogenic markers (BMP2, RUNX2, ALP, OCN) were evaluated. Results: Pressure at 2 g/cm ² for 4 h optimally induced osteoclastogenesis and inflammation. Lira did not affect Piezo1 expression but significantly suppressed NFATc1 and TRAP at both mRNA and protein levels. Lira also inhibited the TRAF6-NF-κB pathway, reducing TNF-α, iNOS, and IL-1β expression. Conditioned media from Lira-treated macrophages significantly upregulated BMP2, RUNX2, ALP, and OCN in MC3T3-E1 cells, indicating indirect promotion of osteogenesis. Conclusion: Liraglutide reverses pressure-induced bone metabolic imbalance through a triple mechanism: inhibiting osteoclastogenesis, attenuating inflammation, and indirectly promoting osteogenesis via macrophage modulation. This study provides the first evidence of liraglutide’s molecular network in regulating bone metabolism under mechanical stress, supporting its therapeutic potential in pressure-related degenerative joint diseases such as osteoarthritis and temporomandibular joint osteoarthritis.
SN - 1663-9812
ER -