Systemic Inflammation Affects Human Osteocyte-Specific Protein and Cytokine Expression.

Area of Science:

• Bone Biology
• Rheumatology
• Cellular and Molecular Medicine

Background:

• Rheumatoid arthritis (RA) can disrupt bone remodeling, potentially due to elevated inflammatory cytokines.
• Osteocytes, crucial cells in bone, produce specific proteins and cytokines that regulate bone formation and resorption.
• Understanding osteocyte responses to RA is vital for addressing bone loss in this condition.

Purpose of the Study:

• To investigate the impact of RA serum and inflammatory cytokines on the expression of human osteocyte-specific proteins and cytokines.
• To determine if osteocytes are affected by the inflammatory environment characteristic of active RA.

Main Methods:

• Human trabecular bone chips were cultured with RA serum or specific inflammatory cytokines (IL-1β, TNFα, IL-8) for 7 days.
• Cell viability was assessed using live-dead staining.
• Gene expression of osteocyte markers (SOST, FGF23, DMP1, MEPE) and cytokines (IL-1β, IL-6, TNFα) was analyzed via qPCR and immunostaining.

Main Results:

• Osteocytes expressed key genes like SOST, FGF23, DMP1, and MEPE, along with cytokines IL-1β, IL-6, and TNFα.
• RA serum significantly upregulated IL-1β, TNFα, SOST, and DKK1 gene expression.
• Treatment with IL-1β, TNFα, or a combination of IL-1β, IL-6, and TNFα modulated the expression of multiple osteocyte genes and cytokines, with the combination synergistically upregulating some and inhibiting others (DKK1).

Conclusions:

• Osteocyte gene expression of specific proteins and cytokines is demonstrably affected by RA serum and exogenous inflammatory cytokines.
• These findings highlight the role of osteocytes in the bone's response to systemic inflammation in RA.
• Osteocytes represent a potential therapeutic target for mitigating inflammation-induced bone loss in rheumatoid arthritis.