The Effects of Calcitonin Gene-Related Peptide on Bone Homeostasis and Regeneration

AbstractPurpose of ReviewThe goals of this review are two folds: (1) to describe the recent understandings on the roles of calcitonin gene-related peptide- α (CGRP) in bone homeostasis and the underlying mechanisms of related neuronal regulation and (2) to propose innovative CGRP-modulated approaches for enhancing bone regeneration in challenging bone disorders.Recent FindingsCGRP is predominantly produced by the densely distributed sensory neuronal fibers in bone, declining with age. Under mechanical and biochemical stimulations, CGRP releases and exerts either physiological or pathophysiological roles. CGRP at physiological level orchestrates the communications of bone cells with cells of other lineages, affecting not only osteogenesis, osteoclastogenesis, and adipogenesis but also angiogenesis, demonstrating with pronounced anabolic effect, thus is essential for maintaining bone homeostasis, with tuned nerve-vessel-bone network. In addition, its effects on immunity and cell recruitment are also crucial for bone fracture healing. Binding to the G protein-coupled receptor composited by calcitonin receptor-like receptor (CRLR) and receptor activity modifying protein 1 (RAMP1) on cellular surface, CGRP triggers various intracellular signaling cascades involving cyclic adenosine monophosphate (cAMP) and cAMP response element-binding protein (CREB). Peaking at early stage post-fracture, CGRP promotes bone formation, displaying with larger callus. Then CGRP gradually decreases o...
Source: Current Osteoporosis Reports - Category: Orthopaedics Source Type: research