Dual functions of microRNA-17 in maintaining cartilage homeostasis and protection against osteoarthritis

Nature Communications, 2022 · DOI: https://doi.org/10.1038/s41467-022-30119-8 · Published: May 6, 2022

Simple Explanation

This study investigates the role of miR-17, a small RNA molecule, in maintaining healthy cartilage and protecting against osteoarthritis (OA). The researchers found that miR-17 levels are reduced in OA cartilage, contributing to disease progression. They showed that increasing miR-17 levels, either by directly adding it or by stimulating its production with a growth factor called GDF-5, can prevent OA by targeting enzymes that break down cartilage. The study also identified different types of cells in cartilage and found that miR-17 helps maintain a balance between cartilage breakdown and repair, potentially by controlling a protein called HIF-1α.

Study Duration

Up to 12 weeks

Participants

Male C57BL/6J mice, human cartilage samples from 6 patients without arthritis and 18 patients with OA

Evidence Level

Not specified

Key Findings

1
MiR-17 expression is decreased in osteoarthritic chondrocytes, and its deficiency contributes to OA progression.
2
Supplementation of exogenous miR-17 or its endogenous induction by growth differentiation factor 5 effectively prevented OA by simultaneously targeting pathological catabolic factors.
3
Single-cell RNA sequencing revealed distinct superficial chondrocyte populations, and miR-17 maintains the physiological catabolic and anabolic balance by restricting HIF-1α signaling.

Research Summary

The study demonstrates that miR-17 has dual functions: maintaining cartilage homeostasis and protecting against OA. Decreased miR-17 expression in OA chondrocytes contributes to disease progression. Increasing miR-17 levels, either exogenously or through GDF-5 induction, effectively prevents OA by targeting multiple catabolic factors like MMP3/13, ADAMTS5, and NOS2. Single-cell RNA sequencing reveals that miR-17 is highly expressed in superficial and middle chondrocytes, maintaining physiological catabolic and anabolic balance, potentially by restricting HIF-1α signaling.

Practical Implications

Therapeutic Target for OA

MiR-17 could be a potential drug target for OA. Supplementation of miR-17 might be a potent therapeutic approach for OA as well as prevention of cartilage aging.

Understanding Cartilage Homeostasis

The study provides insights into the molecular mechanisms underlying cartilage homeostasis and the role of miR-17 in maintaining this balance.

Personalized OA Treatment

Identifying different chondrocyte populations and their specific responses to miR-17 could lead to personalized treatment strategies for OA.

Study Limitations

1
The study primarily used a mouse model of OA, and further research is needed to confirm these findings in humans.
2
The precise mechanisms by which miR-17 regulates HIF-1α signaling and other downstream targets require further investigation.
3
The study does not fully elucidate the potential roles of other members of the miR-17~92 cluster in cartilage homeostasis and OA progression.

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