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

Abstract

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.

Drug discovery in spinal cord injury-induced osteoporosis: a text mining-based study

“…RANKL could promote osteoblast proliferation and activation via binding to its receptor RANK, while OPG acted as a receptor to bind with RANKL, thus preventing the activation of RANK. Following SCI, RANKL was upregulated by binding to the RANK receptor on osteoclastogenesis, thus leading to OP ( 58 ). These findings suggest that the RANK/RANKL/OPG axis provides a means of coupling the activities of osteoblasts and osteoclasts and controlling the balance between bone formation and resorption ( 59 ).…”