695: PDRN Promotes Bone Regeneration via Enhanced Osteoblast Differentiation and Mineralization

Topic: Experimental (Non-clinical) Human Studies
Subtopic: Non -specific to any diagnosis, Pharmacological treatments, Molecular markers

Background and Aims: Developing novel anabolic agents for bone regeneration is a clinical priority due to the adverse effects and limited long-term efficacy of existing treatments. Polydeoxyribonucleotide (PDRN), a tissue-regenerative agent widely used in chronic pain management, has shown promise in tissue repair; however, its specific mechanisms within bone metabolism remain poorly understood. This study aimed to elucidate the direct cellular effects and molecular mechanisms of PDRN on osteoblasts and osteoclasts and to evaluate its therapeutic efficacy in an in vivo osteoporosis model.

Methods: The effects of PDRN on osteoblast (MC3T3-E1) and osteoclast (BMMs) differentiation were evaluated using ALP/ARS and TRAP/resorption assays. Molecular mechanisms were analyzed via qRT-PCR and Western blotting for osteogenic markers (Runx2, Osteocalcin). In vivo, osteoporosis was induced by bilateral ovariectomy (OVX) in mice. Subjects were treated with PDRN (8 or 16 mg/kg, IP) or saline for 8 weeks. Following sacrifice, femoral bone mineral density (BMD) and micro-architecture were analyzed using micro-CT to determine PDRN’s regenerative potential.

Results: PDRN inhibited osteoblast proliferation in a dose-dependent manner but significantly upregulated early Runx2 expression. Enhanced differentiation was confirmed by increased ALP activity and marked mineralized matrix deposition in ARS staining. Osteogenic markers, including Runx2 and osteocalcin, were significantly upregulated at both mRNA and protein levels. Conversely, PDRN had no direct effect on osteoclast viability or differentiation. In vivo micro-CT analysis revealed that the 8 mg/kg PDRN dose significantly increased bone volume/total volume (BV/TV) compared to the OVX control group.

Conclusions: Our findings demonstrate that PDRN acts as a potent anabolic agent, promoting bone regeneration primarily by enhancing osteoblast differentiation and mineralization rather than cellular proliferation. Importantly, PDRN showed significant in vivo efficacy in improving bone micro-architecture in an osteoporosis model at a specific dose. These results suggest that PDRN, already established in clinical pain practice, holds significant potential as a novel therapeutic strategy for metabolic bone diseases and associated chronic pain conditions.

References: [1] L.G. Raisz, Pathogenesis of osteoporosis: concepts, conflicts, and prospects, J Clin Invest 115 (2005) 3318-3325. 10.1172/jci27071.
[2] C.W.S. Hoong, D. Saul, S. Khosla, J.G. Sfeir, Advances in the management of osteoporosis, BMJ 390 (2025) e081250. 10.1136/bmj-2024-081250.
[3] P. Rabbani, B. Ramkhelawon, B.N. Cronstein, Adenosine metabolism and receptors in aging of the skin, musculoskeletal, immune and cardiovascular systems, Ageing Res Rev 106 (2025) 102695. 10.1016/j.arr.2025.102695.
[4] S. Guizzardi, C. Galli, P. Govoni, R. Boratto, G. Cattarini, D. Martini, S. Belletti, R. Scandroglio, Polydeoxyribonucleotide (PDRN) promotes human osteoblast proliferation: a new proposal for bone tissue repair, Life Sci 73 (2003) 1973-1983. 10.1016/s0024-3205(03)00547-2.
[5] A. Mediero, T. Wilder, M. Perez-Aso, B.N. Cronstein, Direct or indirect stimulation of adenosine A2A receptors enhances bone regeneration as well as bone morphogenetic protein-2, Faseb j 29 (2015) 1577-1590. 10.1096/fj.14-265066.

Presenting Author: Jinyoung Oh
Submitting Author: Jinyoung Oh

Senior Author: Younghoon Jeon

IASP 2026 Global Year theme of Neuropathic Pain: No

• Younghoon Jeon: M.D., Ph.D., - Department of Anesthesiology and Pain Medicine, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea