The Role of the Immune Microenvironment on Osteoblast Differentiation

BACKGROUND: Osteoblasts, derived from mesenchymal stem cells (MSCs) in the bone marrow, are responsible for bone formation. Osteoblast differentiation is orchestrated by a spectrum of biological signals, with immune-derived components serving as indispensable regulators in this network. Dysfunctional osteoblast differentiation underlies bone-related pathologies such as osteoarthritis, rheumatoid arthritis, and osteoporosis, where immune dysregulation drives inflammatory cascades that disrupt the osteoblast-osteoclast equilibrium. This bidirectional crosstalk has propelled the emergence of osteoimmunology as a pivotal discipline. METHODS: By analyzing immune cells and cytokines in the immune microenvironment, we synthesize evidence on their roles in regulating osteoblast differentiation, with focus on inflammatory bone disorders, particularly in osteoarthritis. RESULTS: Thus, bone growth, development, and healing are intrinsically coupled with the dynamics of the immune microenvironment, which contributes to subchondral bone sclerosis and disease progression in osteoarthritis. Therefore, targeting immune-osteoblast crosstalk offers therapeutic potential for bone pathologies. CONCLUSION: This review consolidates recent advances in understanding how the immune microenvironment impacts osteoblast differentiation, aiming to provide novel insights for clinical strategies targeting bone repair and disease mitigation.