The role of toll-like receptors in orchestrating osteogenic differentiation of mesenchymal stromal cells and osteoimmunology

Xiaoyang Liu; Zongke Zhou; Wei-Nan Zeng; Qin Zeng; Xingdong Zhang

doi:10.3389/fcell.2023.1277686

The role of toll-like receptors in orchestrating osteogenic differentiation of mesenchymal stromal cells and osteoimmunology

Front Cell Dev Biol. 2023 Oct 23:11:1277686. doi: 10.3389/fcell.2023.1277686. eCollection 2023.

Authors

Xiaoyang Liu¹, Zongke Zhou¹, Wei-Nan Zeng¹, Qin Zeng^{2

3}, Xingdong Zhang^{2

3}

Affiliations

¹ Orthopedic Research Institution, Department of Orthopedics, West China Hospital, Sichuan University, Chengdu, China.
² National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, China.
³ NMPA Key Laboratory for Quality Research and Control of Tissue Regenerative Biomaterials & Institute of Regulatory Science for Medical Devices & NMPA Research Base of Regulatory Science for Medical Devices, Sichuan University, Chengdu, China.

Abstract

Osteoimmunology is a concept involving molecular and cellular crosstalk between the skeletal and immune systems. Toll-like receptors (TLRs) are widely expressed both on mesenchymal stromal cells (MSCs), the hematopoietic cells, and immune cells in the osteogenic microenvironment for bone development or repair. TLRs can sense both exogenous pathogen-associated molecular patterns (PAMPs) derived from microorganisms, and damage-associated molecular patterns (DAMPs) derived from normal cells subjected to injury, inflammation, or cell apoptosis under physiological or pathological conditions. Emerging studies reported that TLR signaling plays an important role in bone remodeling by directly impacting MSC osteogenic differentiation or osteoimmunology. However, how to regulate TLR signaling is critical and remains to be elucidated to promote the osteogenic differentiation of MSCs and new bone formation for bone tissue repair. This review outlines distinct TLR variants on MSCs from various tissues, detailing the impact of TLR pathway activation or inhibition on MSC osteogenic differentiation. It also elucidates TLR pathways' interplay with osteoclasts, immune cells, and extracellular vesicles (EVs) derived from MSCs. Furthermore, we explore biomaterial-based activation to guide MSCs' osteogenic differentiation. Therefore, understanding TLRs' role in this context has significant implications for advancing bone regeneration and repair strategies.

Keywords: biomaterials; extracellular vesicles; mesenchymal stromal cells; osteogenic differentiation; toll-like receptors.

Publication types

Review

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work is supported by National Natural Science Foundation of China (grant No. 32171333, 82272483) and Fundamental Research Funds for the Central Universities (SCU2023YLQX).