Study discloses molecular mechanism of oligodendrocyte myelination by osteocalcin in the CNS

Osteocalcin (OCN) is a multifunctional bone-derived hormone that modulates numerous physiological activities. OCN can cross the blood brain barrier (BBB) and thus play critical roles in neuronal and brain development.

Fully elucidating the exact function of OCN in the central nervous system (CNS) is significant for the discovery of therapeutic targets in treating CNS disorders.

A research team led by LI Xiang from the Shenzhen Institute of Advanced Technology (SIAT) of the Chinese Academy of Sciences has revealed the molecular mechanism of oligodendrocyte myelination by OCN in the CNS.

Their study was published in Science Advances on Oct. 22.

The researchers first investigated the effects of OCN on CNS myelination using an OCN-deficient mouse model. By combining immunostaining, western blotting and electron microscopy analysis, they found that OCN deletion results in hypermyelination in the CNS.

Oligodendrocytes (OLs) are glial cells that form myelin in the CNS. To clarify the mechanism of OCN in CNS myelination, the researchers further investigated whether OCN plays a role in regulation of OL differentiation and myelination.

By using an OCN-deficient mouse model, primary OL culture and exogenous OCN treatment, they found that genetic deletion of OCN facilitated OL differentiation and hypermyelination through the transcription factor Myrf in the CNS. Although dispensable for the proliferation of oligodendrocyte precursor cells (OPCs), OCN was critical for the myelination of OLs, which affected myelin production and remyelination after demyelinating injury.

To identify the receptor for OCN in OLs, the researchers combined RNA sequencing, heterologous systems biophysical analysis, and in vivo mouse model validation, and finally proved that GPR37 is the receptor for OCN and mediates its function in OLs.

These findings not only identify a new role for the OCN hormone in the CNS, but also demonstrate a molecular basis for the function of OCN by activation of GPR37 signaling. This study provides a unique perspective for understanding the mutual communication between skeletal biology and glial functions.

Journal reference:

Qian, Z., et al. (2021) Osteocalcin attenuates oligodendrocyte differentiation and myelination via GPR37 signaling in the mouse brain. Science Advances.


The opinions expressed here are the views of the writer and do not necessarily reflect the views and opinions of News Medical.
Post a new comment

While we only use edited and approved content for Azthena answers, it may on occasions provide incorrect responses. Please confirm any data provided with the related suppliers or authors. We do not provide medical advice, if you search for medical information you must always consult a medical professional before acting on any information provided.

Your questions, but not your email details will be shared with OpenAI and retained for 30 days in accordance with their privacy principles.

Please do not ask questions that use sensitive or confidential information.

Read the full Terms & Conditions.

You might also like...
European Hormone Day 2024 puts spotlight on the vital role of hormones in chronic diseases