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Related Experiment Video

Updated: Jul 8, 2026

Parallel Measurement of Circadian Clock Gene Expression and Hormone Secretion in Human Primary Cell Cultures

Parallel Measurement of Circadian Clock Gene Expression and Hormone Secretion in Human Primary Cell Cultures

Published on: November 11, 2016

An Integrated Approach Reveals the Pre-Osteoblast-Driven Metrnl Synergizes With Circadian Genes to Inhibit

Wenchao Fei¹, Ke Xu¹, MingMing Xu¹

¹Department of Orthopedics, The Fifth People's Hospital of Shanghai, Fudan University, 200040 Shanghai, China.

Frontiers in Bioscience (Landmark Edition)

|July 7, 2026

Summary

Meteorin-like (Metrnl) negatively regulates bone formation by inhibiting osteoblast differentiation. Targeting this pathway offers a new anabolic strategy for osteoporosis treatment.

Keywords:

Metrnl Rack1-PKCα-Bmal1-Cry2 axis osteogenesis osteoporosis (OP)therapeutic target

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Multimodal Approach to Assess Bone Regeneration and Scaffold Performance

Multimodal Approach to Assess Bone Regeneration and Scaffold Performance

Published on: February 13, 2026

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Last Updated: Jul 8, 2026

Parallel Measurement of Circadian Clock Gene Expression and Hormone Secretion in Human Primary Cell Cultures

Parallel Measurement of Circadian Clock Gene Expression and Hormone Secretion in Human Primary Cell Cultures

Published on: November 11, 2016

Multimodal Approach to Assess Bone Regeneration and Scaffold Performance

Multimodal Approach to Assess Bone Regeneration and Scaffold Performance

Published on: February 13, 2026

Area of Science:

Skeletal Biology
Endocrinology
Chronobiology

Background:

Current osteoporosis therapies focus on bone resorption inhibition, creating a need for anabolic bone formation strategies.
The role of Meteorin-like (Metrnl), an adipokine, in bone metabolism is not well understood.
This study investigates Metrnl's expression, function, and molecular mechanisms in skeletal biology.

Purpose of the Study:

To elucidate the role of Meteorin-like (Metrnl) in bone metabolism.
To investigate the molecular mechanisms by which Metrnl influences osteogenesis.
To explore the potential of Metrnl-related pathways for osteoporosis therapy.

Main Methods:

Analysis of clinical bone marrow samples and proteomics.
Single-cell RNA sequencing and conditional genetic ablation mouse models.
Micro-CT, bone histomorphometry, co-immunoprecipitation, and transcriptional assays.

Main Results:

Metrnl expression is decreased in postmenopausal osteoporosis patients and declines with age in mice.
Metrnl knockout mice exhibit increased bone mass and formation rates, indicating an inhibitory role in osteogenesis.
Metrnl interacts with Rack1, disrupting the PKCα-Rack1 complex, reducing Bmal1 phosphorylation, and upregulating Cry2 to suppress osteoblast differentiation.

Conclusions:

Metrnl acts as a negative regulator of bone formation.
A novel signaling axis (Rack1-PKCα-Bmal1-Cry2) links circadian regulation to osteogenesis.
Targeting Metrnl pathways presents a potential anabolic therapeutic strategy for osteoporosis.