Gene Expression in Osteoblasts and Osteoclasts Under Microgravity Conditions: A Systematic Review

Area of Science:

• Space biology
• Cellular biology
• Bone metabolism

Background:

• Microgravity negatively impacts bone metabolism by altering osteoblast and osteoclast function.
• Understanding these effects is crucial for mitigating challenges of space flight.

Purpose of the Study:

• To systematically review genomic studies on osteoblast and osteoclast cells in microgravity.
• To elucidate the molecular mechanisms underlying microgravity's effects on bone cells.

Main Methods:

• Systematic review of 50 genomic studies on osteoblast and osteoclast cells in real or simulated microgravity.
• Analysis of gene expression and protein markers related to bone cell differentiation and activity.

Main Results:

• Microgravity decreases osteoblast differentiation, evidenced by reduced Alkaline Phosphatase (ALP) and Osteocalcin (OCN) expression.
• Increased Receptor Activator of NF-κB Ligand (RANKL)/Osteoprotegerin (OPG) ratio and Interleukin-6 (IL-6) upregulation indicate enhanced osteoclastogenesis.
• Mechanotransduction pathways (MAPK, AP-1, NF-κB) are implicated in mediating microgravity's effects on nuclear transcription factors.
• Pre-osteoclastic cells exhibit increased expression of TRAP, cathepsin K, and MMP-9, becoming more sensitive to RANKL.

Conclusions:

• Microgravity-induced bone cell dysfunction involves complex signaling pathways.
• Fusion genes like syncytin-A, independent of RANKL, represent potential therapeutic targets for mitigating microgravity's adverse effects on bone.