Honokiol, a structurally defined natural product, promotes SIRT3-linked bone formation in osteoporotic bone remodeling and fracture repair.
- 1Department of Ultrasound Medicine, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, China.
- 2Hunan Provincial Key Laboratory of Multi-omics and Artificial Intelligence of Cardiovascular Diseases, University of South China, Hengyang, China.
- 3Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, China.
Abstract
Context
Honokiol is a structurally defined biphenolic natural product with reported mitochondrial and cytoprotective activities. Whether honokiol modifies pathological skeletal remodeling through sirtuin 3 (SIRT3)-linked mechanisms remains unclear.Objective
This study investigated whether honokiol regulates bone cell lineage responses and improves osteoporotic bone remodeling and fracture repair through SIRT3-associated bone formation.Materials and methods
Mouse bone marrow-derived mesenchymal stem cells and RAW264.7 cells were used to assess osteogenesis, adipogenesis, and osteoclastogenesis after recombinant SIRT3, honokiol, or SIRT3 siRNA transfection. In vivo effects were examined in ovariectomized mice and stabilized femoral fracture models. Local AAV-shSIRT3 delivery was used to evaluate target dependence. Outcomes included micro-computed tomography, histology, osteocalcin immunohistochemistry, calcein double labeling, and three-point bending analysis.Results
Recombinant SIRT3 enhanced osteogenic mineralization and suppressed adipogenic differentiation and osteoclastogenesis. Honokiol increased SIRT3 expression and produced a similar lineage-shifting profile. SIRT3 knockdown markedly attenuated honokiol-induced osteogenesis, whereas its anti-adipogenic and anti-osteoclastogenic effects were only partly reduced. In ovariectomized mice, honokiol improved trabecular microarchitecture, mineral apposition, osteoblast activity, and femoral strength while reducing marrow adiposity and osteoclast burden. In fractured femora, honokiol increased mineralized callus formation, osteoblast activity, and biomechanical recovery. Local AAV-shSIRT3 intervention weakened these benefits, particularly for bone-forming and structural endpoints.Discussion and conclusion
Honokiol demonstrates a preclinical skeletal pharmacological profile characterized by predominantly SIRT3-linked bone formation. Its broader effects on adipogenic and osteoclast-associated responses appear only partly SIRT3-dependent.
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BibTeX
@article{xie2026honokiol,
title = {{Honokiol, a structurally defined natural product, promotes SIRT3-linked bone formation in osteoporotic bone remodeling and fracture repair.}},
author = {Shanshan Xie and Changbiao Guan and Jia Zhou},
journal = {Pharmaceutical biology},
year = {2026},
month = oct,
doi = {10.1080/13880209.2026.2729885},
url = {https://europepmc.org/article/MED/42852533},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - Honokiol, a structurally defined natural product, promotes SIRT3-linked bone formation in osteoporotic bone remodeling and fracture repair.
AU - Shanshan Xie
AU - Changbiao Guan
AU - Jia Zhou
PY - 2026
DA - 2026/10/09
JO - Pharmaceutical biology
DO - 10.1080/13880209.2026.2729885
UR - https://europepmc.org/article/MED/42852533
AB - Context Honokiol is a structurally defined biphenolic natural product with reported mitochondrial and cytoprotective activities. Whether honokiol modifies pathological skeletal remodeling through sirtuin 3 (SIRT3)-linked mechanisms remains unclear.Objective This study investigated whether honokiol regulates bone cell lineage responses and improves osteoporotic bone remodeling and fracture repair through SIRT3-associated bone formation.Materials and methods Mouse bone marrow-derived mesenchymal stem cells and RAW264.7 cells were used to assess osteogenesis, adipogenesis, and osteoclastogenesis after recombinant SIRT3, honokiol, or SIRT3 siRNA transfection. In vivo effects were examined in ovariectomized mice and stabilized femoral fracture models. Local AAV-shSIRT3 delivery was used to evaluate target dependence. Outcomes included micro-computed tomography, histology, osteocalcin immunohistochemistry, calcein double labeling, and three-point bending analysis.Results Recombinant SIRT3 enhanced osteogenic mineralization and suppressed adipogenic differentiation and osteoclastogenesis. Honokiol increased SIRT3 expression and produced a similar lineage-shifting profile. SIRT3 knockdown markedly attenuated honokiol-induced osteogenesis, whereas its anti-adipogenic and anti-osteoclastogenic effects were only partly reduced. In ovariectomized mice, honokiol improved trabecular microarchitecture, mineral apposition, osteoblast activity, and femoral strength while reducing marrow adiposity and osteoclast burden. In fractured femora, honokiol increased mineralized callus formation, osteoblast activity, and biomechanical recovery. Local AAV-shSIRT3 intervention weakened these benefits, particularly for bone-forming and structural endpoints.Discussion and conclusion Honokiol demonstrates a preclinical skeletal pharmacological profile characterized by predominantly SIRT3-linked bone formation. Its broader effects on adipogenic and osteoclast-associated responses appear only partly SIRT3-dependent.
SN - 1388-0209
SN - 1744-5116
ER -