681: Acupuncture improves gait dysfunction and bone formation via ?2-adrenergic receptor signaling

Topic: Experimental (Non-clinical) Human Studies
Subtopic: Pain Category (ICD-11), Acute musculoskeletal pain, Non-pharmacological treatments, Assessment and Measurement of Pain/Nociception, Molecular markers

Background and Aims: Bone defects and fractures involve damage to bone tissue or disruption of structural continuity and are associated with pain and reduced quality of life. Despite surgical treatment, 10–15% of cases result in delayed union or nonunion, highlighting the need for improved therapeutic strategies. The sympathetic nervous system regulates bone remodeling via β2-adrenergic receptor (β2AR) signaling in osteoblasts, promoting RANKL-mediated osteoclastogenesis. Although acupuncture is known to modulate autonomic nervous system activity, its role in bone regeneration and the underlying mechanisms remain unclear.

Methods: The therapeutic effects and mechanisms of acupuncture were investigated using a mouse femoral drill-hole (DH) defect model, in which a standardized monocortical defect (0.5–1 mm in diameter) was created at the mid-diaphysis under isoflurane anesthesia. Acupuncture was applied at GB34 (Yanglingquan) five times per week from 7 days post-injury. Gait function was assessed using footprint analysis at 1 and 2 weeks after treatment. Bone regeneration was evaluated by micro-computed tomography (micro-CT) and histological analysis of the defect site. Immunofluorescence staining was performed to assess osteoblast activity (osteocalcin), osteoclast-related markers (RANKL and RANK), and β2-adrenergic receptor (β2AR) expression. The sympathetic noradrenergic system was evaluated by TH and DBH expression in the femoral bone regions. Also, TH expression in the paraventricular nucleus (PVN).

Results: Behavioral assessment using footprint analysis revealed reduced ipsilateral hind paw foot length in the DH group, which was significantly restored by acupuncture, indicating improved functional recovery. Micro-CT analysis revealed higher BV/TV in the cortical region than in the defect region, suggesting disproportionate cortical bone formation. Acupuncture significantly reduced BV/TV in the cortical region and increased bone formation within the defect region, indicating restoration of balanced bone remodeling. Immunofluorescence analysis revealed increased RANKL expression in osteocalcin-positive osteoblasts, accompanied by elevated RANK and TRAP expression, indicating enhanced osteoclastogenesis, which was suppressed by acupuncture. β2AR expression in osteoblasts was increased in the DH group and attenuated by acupuncture. TH and DBH expression indicated increased sympathetic noradrenergic signaling in femoral bone regions, attenuated by acupuncture. In the PVN, TH expression was increased following injury and attenuated by acupuncture. Correlation analysis showed positive correlations between PVN TH-positive activity and RANKL, β2AR, and RANK.

Conclusions: Acupuncture promotes bone formation by attenuating β2AR–RANKL/RANK-mediated osteoclastogenesis during femoral bone defect repair.

Acknowledgement: This work was supported by the Korea Health Industry Development Institute (Grant No. RS-2023-KH139336).

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Presenting Author: Seok Hee Han
Submitting Author: SEOKHEE HAN

Senior Author: In-Hyuk Ha

IASP 2026 Global Year theme of Neuropathic Pain: Yes

• Jae-Hwan Jang: Ph.D. - Jaseng Spine and Joint Research Institute, Jaseng Medical Foundation
• Seok Hee Han: Master Degree - Jaseng Spine and Joint Research Institute, Jaseng Medical Foundation
• Yoon Jae Lee: Ph.D. - Jaseng Spine and Joint Research Institute, Jaseng Medical Foundation
• In-Hyuk Ha: Ph.D. - Jaseng Spine and Joint Research Institute, Jaseng Medical Foundation