Osteocalcin and glial modulation: emerging perspectives in the bone-brain axis
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Abstract
Decarboxylated osteocalcin, a hormone derived from osteoblasts, crosses the blood-brain barrier and participates in central nervous system homeostasis. This narrative review explores the growing interest, shifting from neuron-centered signaling to its suggested role in glial modulation, based on preclinical and observational evidence. Current evidence supports that osteocalcin exerts neuroprotective effects by binding to the neuronal GPR158 receptor and the glial GPR37 receptor. In murine models, it modulates astrocytic glycophagy, attenuates pro-inflammatory activation of microglia, promotes beta-amyloid (Aβ) clearance, and regulates myelin homeostasis in oligodendrocytes. Osteocalcin is emerging as a relevant osteokine for neuroregeneration. Modulation of the OCN-GPR158/GPR37 axis represents a promising therapeutic approach that requires further clinical validation to mitigate cognitive decline.
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