Does the chronic use of clonidine, an alpha 2 adrenergic agonist, modify the longitudinal bone growth?

• Grant number: 18/02899-4
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: May 01, 2018
• End date: December 31, 2018
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Cecilia Helena de Azevedo Gouveia
• Grantee: Vitor Nunes Torres
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The SNS is known to negatively regulate bone mass, acting via receptor Beta2-adrenergic receptors (B2-AR). Our group demonstrated that alpha2A (a2A-AR) and a2C (a2C-AR) adrenergic receptors also mediate negative actions of the SNS in the bone mass. In addition, we found that mice with isolated gene inactivation of a2A-AR and a2C-AR (a2A-AR-/- and a2C-AR-/-) exhibit lower body length and present important changes in the epiphyseal growth plate (EGP). In tibia organ cultures, we observed that the longitudinal bone growth (LBG) is lower in tibias from a2A-AR-/- and a2C-AR-/- mice, and that the treatment of these tibias with UK, an a2 adrenergic agonist, decreases the number of hypertrophic chondrocytes in the growth plate. These studies show that the SNS modulates the LBG, and that a2A-AR and a2C-AR mediate this action directly into the skeleton. As these findings are unprecedented and yet unknown in the medical practice, possible side effects of the use of a2 adrenergic agonists in bone growth have never been considered. On the other hand, these agonists have been used in clinical practice for decades, for sedation and analgesia, and for the treatment of hypertension, glaucoma, chronic pain and muscular spasticity, in addition to the treatment of behavior disorders such as insomnia, tics and attention deficit hyperactivity disorder (ADHD). Many of these disorders occur in childhood and adolescence and may require chronic use of a2 adrenergic agonists, such as clonidine. Therefore, the present study aims to investigate whether the chronic use of clonidine in mice alters the LBG and the morphology of growth plate. Considering the use of a2 adrenergic agonists in clinical practice, the investigation of possible side effects of chronic therapies with these agonists in the skeletal development becomes quite relevant.