Implications of enolase in the RANKL-mediated osteoclast activity following spinal cord injury

Spinal Cord Injury (SCI) is a debilitating condition characterized by damage to the spinal cord, resulting in loss of function, mobility, and sensation. Although increasingly prevalent in the US, no FDA-approved therapy exists due to the unfortunate complexity of the condition, and the difficulties of SCI may be furthered by the development of SCI-related complications, such as osteoporosis. SCI demonstrates two crucial stages for consideration: the primary stage and the secondary stage. While the primary stage is suggested to be immediate and irreversible, the secondary stage is proposed as a promising window of opportunity for therapeutic intervention. Enolase, a metabolic enzyme upregulated after SCI, performs non-glycolytic functions, promoting inflammatory events via extracellular degradative actions and increased production of inflammatory cytokines and chemokines. Neuron-specific enolase (NSE) serves as a biomarker of functional damage to neurons following SCI, and the inhibition of NSE has been demonstrated to reduce signs of secondary injury of SCI and to ameliorate dysfunction. This Viewpoint article involves enolase activation in the regulation of RANK-RANKL pathway and summarizes succinctly the mechanisms influencing osteoclast-mediated resorption of bone in SCI. Our laboratory proposes that inhibition of enolase activation may reduce SCI-induced inflammatory response and decrease osteoclast activity, limiting the chances of skeletal tissue loss in SCI.