Extracellular Vesicles from Buccal Fat Pad-Derived Dedifferentiated Fat Cells Modulate Inflammatory Macrophage Responses and Attenuate Temporomandibular Joint Osteoarthritis
4 affiliations
- 1Second Department of Oral and Maxillofacial Surgery, Osaka Dental University, 8-1 Kuzuhahanazonocho, Hirakata 573-1121, Osaka, Japan
- 2Division of Biological Chemistry and Biologicals, National Institute of Health Sciences, 3-25-26 Tonomachi, Kawasaki-ku, Kawasaki 210-9501, Kanagawa, Japan
- 3Department of Biomaterials, Osaka Dental University, 8-1 Kuzuhahanazonocho, Hirakata 573-1121, Osaka, Japan
- 4First Department of Oral and Maxillofacial Surgery, Osaka Dental University, 8-1 Kuzuhahanazonocho, Hirakata 573-1121, Osaka, Japan
Abstract
Temporomandibular joint osteoarthritis (TMJ-OA) involves inflammation and degeneration of mandibular condylar cartilage and subchondral bone. Dedifferentiated fat cells (DFATs) were established from buccal fat pad tissue obtained from a single human donor. We examined the effects of DFAT-derived extracellular vesicle preparations (DFAT-EVs) on inflammatory macrophage responses in vitro and disease-related outcomes in TMJ-OA in vivo. DFAT-EVs were applied to lipopolysaccharide- and interferon-γ-stimulated RAW264.7 macrophages and administered intra-articularly in rats with monosodium iodoacetate-induced TMJ-OA. Fluorescence signals from labeled DFAT-EVs were observed in RAW264.7 cells. DFAT-EVs reduced nitric oxide production and modulated nitric oxide synthase 2, interleukin (IL)-1β, IL-6, IL-10, IL-4, and tumor necrosis factor-α responses, although effects varied among inflammatory mediators. Head withdrawal threshold was significantly higher in the DFAT-EVs group than in the OA group at several time points in the 6-week cohort, but not in the 4-week cohort. Administration of DFAT-EVs attenuated the reduction in mandibular condylar bone volume fraction and was associated with preservation of cartilage architecture and matrix. Osteoarthritis Research Society International scores were significantly lower in the DFAT-EVs group than in the OA group at 4 weeks but not at 6 weeks. These in vitro and in vivo findings support further evaluation of DFAT-EVs for TMJ-OA.
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BibTeX
@article{oku2026extracellular,
title = {{Extracellular Vesicles from Buccal Fat Pad-Derived Dedifferentiated Fat Cells Modulate Inflammatory Macrophage Responses and Attenuate Temporomandibular Joint Osteoarthritis}},
author = {Hayato Oku and Yusuke Nishiguchi and Tomofumi Yamamoto and Jun-Ichiro Jo and Yoshiya Hashimoto and Hirohito Kubo and Toshihiko Takenobu},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27209389},
url = {https://www.mdpi.com/1422-0067/27/20/9389},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Extracellular Vesicles from Buccal Fat Pad-Derived Dedifferentiated Fat Cells Modulate Inflammatory Macrophage Responses and Attenuate Temporomandibular Joint Osteoarthritis
AU - Hayato Oku
AU - Yusuke Nishiguchi
AU - Tomofumi Yamamoto
AU - Jun-Ichiro Jo
AU - Yoshiya Hashimoto
AU - Hirohito Kubo
AU - Toshihiko Takenobu
PY - 2026
DA - 2026/10/01
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27209389
UR - https://www.mdpi.com/1422-0067/27/20/9389
AB - Temporomandibular joint osteoarthritis (TMJ-OA) involves inflammation and degeneration of mandibular condylar cartilage and subchondral bone. Dedifferentiated fat cells (DFATs) were established from buccal fat pad tissue obtained from a single human donor. We examined the effects of DFAT-derived extracellular vesicle preparations (DFAT-EVs) on inflammatory macrophage responses in vitro and disease-related outcomes in TMJ-OA in vivo. DFAT-EVs were applied to lipopolysaccharide- and interferon-γ-stimulated RAW264.7 macrophages and administered intra-articularly in rats with monosodium iodoacetate-induced TMJ-OA. Fluorescence signals from labeled DFAT-EVs were observed in RAW264.7 cells. DFAT-EVs reduced nitric oxide production and modulated nitric oxide synthase 2, interleukin (IL)-1β, IL-6, IL-10, IL-4, and tumor necrosis factor-α responses, although effects varied among inflammatory mediators. Head withdrawal threshold was significantly higher in the DFAT-EVs group than in the OA group at several time points in the 6-week cohort, but not in the 4-week cohort. Administration of DFAT-EVs attenuated the reduction in mandibular condylar bone volume fraction and was associated with preservation of cartilage architecture and matrix. Osteoarthritis Research Society International scores were significantly lower in the DFAT-EVs group than in the OA group at 4 weeks but not at 6 weeks. These in vitro and in vivo findings support further evaluation of DFAT-EVs for TMJ-OA.
SN - 1422-0067
ER -