The CX3CL1-CX3CR1 axis in mesenchymal stem cell regulation and bone diseases
- 1School of Basic Medical Sciences, Zunyi Medical University
Abstract
The chemokine axis CX3CL1-CX3CR1 is involved in the whole process of bone remodeling, bone injury repair, and inflammation-mediated bone destruction, making it both a diagnostic marker and a potential target for therapy. This article focuses on bone marrow mesenchymal stem cells (BMSCs) to explain the bidirectional mechanism of CX3CL1-CX3CR1 in regulating bone homeostasis, compares three types of targeting strategies, and proposes a local delivery approach. The regulatory effect of CX3CL1 is concentration-dependent: transient or moderate sCX3CL1 signaling is associated with a pro-repair macrophage phenotype, while persistent pathological elevation promotes M1 polarization and bone resorption; however, direct evidence for the low intramedullary concentration of the M2 axis is limited. This article focuses on analyzing the hormone regulatory pathways of three endocrine-related bone diseases (postmenopausal osteoporosis, diabetic bone disease, and hyperthyroidism-induced bone injury), and compares the advantages and disadvantages of monoclonal antibodies, small molecule drugs, and bone nanocarriers. The CX3CL1-CX3CR1 axis represents a candidate research target for pre-clinical investigations into endocrine-related bone diseases, yet substantial unresolved barriers limit its translational progression. Local targeted delivery strategies may offer conceptual directions for future pre-clinical investigation for solving the treatment challenges brought about by the bidirectional effects of this pathway, but their clinical feasibility still needs to be verified. Notably, critical in-vivo concentration thresholds distinguishing protective versus pathological CX3CL1 effects have not been established, and evidence supporting concentration-dependent M1/M2 macrophage polarization is largely derived from non-bone systems.
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BibTeX
@article{kuang2026cx3cl1cx3cr1,
title = {{The CX3CL1-CX3CR1 axis in mesenchymal stem cell regulation and bone diseases}},
author = {Ziyun Kuang and Yixin Zhang and Jiao Li},
journal = {Frontiers in Endocrinology},
year = {2026},
month = oct,
doi = {10.3389/fendo.2026.1992376},
url = {https://www.frontiersin.org/articles/10.3389/fendo.2026.1992376/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - The CX3CL1-CX3CR1 axis in mesenchymal stem cell regulation and bone diseases
AU - Ziyun Kuang
AU - Yixin Zhang
AU - Jiao Li
PY - 2026
DA - 2026/10/30
JO - Frontiers in Endocrinology
DO - 10.3389/fendo.2026.1992376
UR - https://www.frontiersin.org/articles/10.3389/fendo.2026.1992376/full
AB - The chemokine axis CX3CL1-CX3CR1 is involved in the whole process of bone remodeling, bone injury repair, and inflammation-mediated bone destruction, making it both a diagnostic marker and a potential target for therapy. This article focuses on bone marrow mesenchymal stem cells (BMSCs) to explain the bidirectional mechanism of CX3CL1-CX3CR1 in regulating bone homeostasis, compares three types of targeting strategies, and proposes a local delivery approach. The regulatory effect of CX3CL1 is concentration-dependent: transient or moderate sCX3CL1 signaling is associated with a pro-repair macrophage phenotype, while persistent pathological elevation promotes M1 polarization and bone resorption; however, direct evidence for the low intramedullary concentration of the M2 axis is limited. This article focuses on analyzing the hormone regulatory pathways of three endocrine-related bone diseases (postmenopausal osteoporosis, diabetic bone disease, and hyperthyroidism-induced bone injury), and compares the advantages and disadvantages of monoclonal antibodies, small molecule drugs, and bone nanocarriers. The CX3CL1-CX3CR1 axis represents a candidate research target for pre-clinical investigations into endocrine-related bone diseases, yet substantial unresolved barriers limit its translational progression. Local targeted delivery strategies may offer conceptual directions for future pre-clinical investigation for solving the treatment challenges brought about by the bidirectional effects of this pathway, but their clinical feasibility still needs to be verified. Notably, critical in-vivo concentration thresholds distinguishing protective versus pathological CX3CL1 effects have not been established, and evidence supporting concentration-dependent M1/M2 macrophage polarization is largely derived from non-bone systems.
SN - 1664-2392
ER -