[P3-2-07] Targeted bone growth by local retinoid administration
Keywords:軟骨、骨、レチノイン酸
Growth-plate (GP) injuries may result in impairment of GP function and deceleration of the bone growth, leading to progressive growth imbalance and deformity. In this study, we aimed to develop a pharmacologic treatment that involves local application and controlled release of a nanocarrier-encapsulated synthetic compound selectively targeting the retinoic acid nuclear receptor gamma (RARγ). We demonstrated that systemically administered selective RARγ agonists induced GP closure and inhibited bone growth in juvenile mice. RARα and RARβagonists did not inhibit bone growth. When nanoparticle-encapsulated RARγ agonists were injected in the vicinity of the proximal tibial growth plate at both medial and lateral sites, the GP was closed losing its hypertrophic zone, and the bone length was markedly shortened compared to the contralateral bone treated with drug-free control nanoparticles. When the RARγ agonist-loaded nanoparticles were injected only at the lateral site, the proximal epiphysis of the treated bone tilted to the lateral site, leading to angular deformity. These findings indicate that RARγ agonist-loaded nanoparticles may be used to control function of the targeted GP, potentially offering a clinically viable alternative or supplemental to surgical correction of limb length discrepancy and angular deformities.