CCL7 is a protective factor secreted by mechanically loaded osteocytes.

Area of Science:

• Biochemistry
• Cell Biology
• Orthopedics

Background:

• Osteocytes are crucial mechanosensors in bone.
• Mechanical loading influences osteocyte viability and function.
• Chemokines play roles in cell signaling and survival.

Purpose of the Study:

• Identify factors upregulated by mechanical strain in osteocytes.
• Investigate the role of chemokine (C-C motif) ligand 7 (CCL7) in osteocyte response to mechanical stress.
• Determine the protective mechanisms of CCL7 against cell death.

Main Methods:

• Utilized MLO-Y4 osteocyte-like cells and in vivo tooth movement models.
• Measured CCL7 expression in response to mechanical strain (fluid flow shear stress).
• Assessed cell viability using dexamethasone and etoposide treatments; employed CCL7 specific antibody and indomethacin.
• Analyzed the β-catenin pathway activation via GSK-3 phosphorylation.

Main Results:

• CCL7 was highly expressed in MLO-Y4 cells and increased in osteocytes during tooth movement.
• CCL7 demonstrated protective effects against dexamethasone- and etoposide-induced cell death.
• CCL7 antibody and indomethacin abrogated fluid flow shear stress-induced protection.
• CCL7 activated the β-catenin pathway, mediated by GSK-3 phosphorylation.
• CCL2, though not mechanically regulated, showed potent protective effects against multiple death inducers.

Conclusions:

• Mechanically induced CCL7 selectively protects osteocytes from glucocorticoid-induced cell death via the β-catenin pathway.
• CCL7 plays an autocrine role in maintaining osteocyte viability under mechanical stress.
• CCL2 may have broader protective functions in osteocytes, independent of mechanical loading.