Amelogenin-derived peptide-5 suppresses the receptor activator of nuclear factor-κB ligand-induced osteoclast differentiation via adenosine monophosphate-activated protein kinase activation
Abstract
Pathological root resorption is mediated by odontoclasts, which share functional characteristics with osteoclasts. However, the effect of amelogenin-derived peptide-5 (ADP-5) on osteoclast differentiation remains unclear. Objective This study aimed to determine whether ADP-5 inhibits the receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation and to explain the involvement of adenosine monophosphate-activated protein kinase (AMPK). Methodology Bone marrow-derived macrophages were isolated from six-week-old mice from the Institute of Cancer Research. Cell viability was assessed. Osteoclast differentiation was induced with RANKL (100 ng/mL) and macrophage colony-stimulating factor (30 ng/mL) in the presence of ADP-5 (0–20 μM). Multinucleated cells were quantified by tartrate-resistant acid phosphatase (TRAP) staining. Osteoclast-specific marker expression (cellular proto-oncogene Fos, cathepsin K, nuclear factor of activated T-cells cytoplasmic 1, and TRAP) was analyzed via quantitative real-time polymerase chain reaction and Western blot. Bone resorption activity was evaluated using a calcium phosphate-coated pit assay. AMPK phosphorylation was examined to assess the associated signaling pathway. Results ADP-5 showed no effect on cell viability. It reduced TRAP-positive multinucleated cell formation and the mRNA and protein expression of key osteoclastogenic markers. Resorptive activity was significantly reduced in ADP-5-treated cells. In parallel, ADP-5 enhanced AMPK phosphorylation during differentiation. Conclusions ADP-5 suppressed RANKL-induced osteoclastogenesis and resorptive activity and was associated with enhanced AMPK phosphorylation. These findings identify ADP-5 as a potential modulator of RANKL-induced osteoclastogenesis and provide a rationale for further investigation of its effects and underlying mechanisms in inflammatory root resorption models.
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BibTeX
@article{koo2026amelogeninderived,
title = {{Amelogenin-derived peptide-5 suppresses the receptor activator of nuclear factor-κB ligand-induced osteoclast differentiation via adenosine monophosphate-activated protein kinase activation}},
author = {Hye-Yoon Koo and Suk-Gyun Park and Ju-Han Song and Jeong-Tae Koh and Sang-Hwa Park and Bin-Na Lee and Hoon-Sang Chang and In-Nam Hwang and Kkot-Byeol Bae and Yun-Chan Hwang},
journal = {Journal of Applied Oral Science},
year = {2026},
month = oct,
doi = {10.1590/1678-7765-2026-0347},
url = {https://doi.org/10.1590/1678-7765-2026-0347},
note = {CC BY},
}
RIS
TY - JOUR
TI - Amelogenin-derived peptide-5 suppresses the receptor activator of nuclear factor-κB ligand-induced osteoclast differentiation via adenosine monophosphate-activated protein kinase activation
AU - Hye-Yoon Koo
AU - Suk-Gyun Park
AU - Ju-Han Song
AU - Jeong-Tae Koh
AU - Sang-Hwa Park
AU - Bin-Na Lee
AU - Hoon-Sang Chang
AU - In-Nam Hwang
AU - Kkot-Byeol Bae
AU - Yun-Chan Hwang
PY - 2026
DA - 2026/10/27
JO - Journal of Applied Oral Science
DO - 10.1590/1678-7765-2026-0347
UR - https://doi.org/10.1590/1678-7765-2026-0347
AB - Pathological root resorption is mediated by odontoclasts, which share functional characteristics with osteoclasts. However, the effect of amelogenin-derived peptide-5 (ADP-5) on osteoclast differentiation remains unclear. Objective This study aimed to determine whether ADP-5 inhibits the receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation and to explain the involvement of adenosine monophosphate-activated protein kinase (AMPK). Methodology Bone marrow-derived macrophages were isolated from six-week-old mice from the Institute of Cancer Research. Cell viability was assessed. Osteoclast differentiation was induced with RANKL (100 ng/mL) and macrophage colony-stimulating factor (30 ng/mL) in the presence of ADP-5 (0–20 μM). Multinucleated cells were quantified by tartrate-resistant acid phosphatase (TRAP) staining. Osteoclast-specific marker expression (cellular proto-oncogene Fos, cathepsin K, nuclear factor of activated T-cells cytoplasmic 1, and TRAP) was analyzed via quantitative real-time polymerase chain reaction and Western blot. Bone resorption activity was evaluated using a calcium phosphate-coated pit assay. AMPK phosphorylation was examined to assess the associated signaling pathway. Results ADP-5 showed no effect on cell viability. It reduced TRAP-positive multinucleated cell formation and the mRNA and protein expression of key osteoclastogenic markers. Resorptive activity was significantly reduced in ADP-5-treated cells. In parallel, ADP-5 enhanced AMPK phosphorylation during differentiation. Conclusions ADP-5 suppressed RANKL-induced osteoclastogenesis and resorptive activity and was associated with enhanced AMPK phosphorylation. These findings identify ADP-5 as a potential modulator of RANKL-induced osteoclastogenesis and provide a rationale for further investigation of its effects and underlying mechanisms in inflammatory root resorption models.
SN - 1678-7765
SN - 1678-7757
ER -