The balance between helper T 17 and regulatory T cells in osteoimmunology and relevant research progress on bone tissue engineering

Abstract

Background: Bone regeneration is a well-regulated dynamic process, of which the prominent role of the immune system on bone homeostasis is more and more revealed by recent research. Before fully activation of the bone remodeling cells, the immune system needs to clean up the microenvironment in facilitating the bone repair initiation. Furthermore, this microenvironment must be maintained properly by various mechanisms over the entire bone regeneration process.

Objective: This review aims to summarize the role of the T-helper 17/Regulatory T cell (Th17/Treg) balance in bone cell remodeling and discuss the relevant progress in bone tissue engineering.

Results: The role of the immune response in the early stages of bone regeneration is crucial, especially the impact of the Th17/Treg balance on osteoclasts, mesenchymal stem cells (MSCs), and osteoblasts activity. By virtue of these knowledge advancements, innovative approaches in bone tissue engineering, such as nano-structures, hydrogel, and exosomes, are designed to influence the Th17/Treg balance and thereby augment bone repair and regeneration.

Conclusion: Targeting the Th17/Treg balance is a promising innovative strategy for developing new treatments to enhance bone regeneration, thus offering potential breakthroughs in bone injury clinics.

Keywords: T‐helper 17 cells; bone tissue engineering; cell balance; osteoimmunology; regulatory T cells.

Figure 1

The balance between Th17 and Treg in osteoimmunology. In the intricate interplay of osteoimmunology, the scales of bone dynamics oscillate between the pro‐inflammatory implication of Th17 and the anti‐inflammatory influence of Treg. Th17 fosters osteoclastogenesis and bone resorption by emitting inflammatory cytokines, such as IL‐17 and TNF‐α, which mainly stimulate the RANKL/RANK pathway and suppress osteoblast activity. Conversely, Treg promotes bone formation by releasing cytokines such as IL‐10 and TGF‐β, activating osteoblast‐related signaling pathways including MAPK, Smad, Wnt, and PI3K/AKT/mTOR/S6. Additionally, Treg impedes osteoclast activity by inducing the apoptosis of their precursors and elevating OPG levels to inhibit RANKL from engaging with RANK. The delicate balance between Th17 and Treg determines the overall inflammatory milieu, which in turn dictates whether bone remodeling leans towards resorption or regeneration.