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Non-coding RNA modulation in osteoclasts and its implications for osteoblast lineage cell behavior in a co-culture
Sara Reis Moura1,2, Jacob Bastholm Olesen3,4, Martin Lindberg-Larsen5,6
1i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal.
Cell Communication and Signaling : CCS
|August 13, 2025
Summary
Non-coding RNAs (ncRNAs) like DLEU1 and miR-16 regulate osteoclast (OC) behavior, influencing bone health. Targeting these ncRNAs in OCs impacts osteoblast (OB) activity and bone remodeling, offering therapeutic potential for bone disorders.
Area of Science:
- Bone biology and skeletal health
- Cellular communication in bone remodeling
- Non-coding RNA regulation in osteoclasts and osteoblasts
Background:
- The balance between osteoblasts (OBs) and osteoclasts (OCs) is crucial for bone integrity, with disruptions leading to disorders like osteoporosis.
- Non-coding RNAs (ncRNAs) have been identified as regulators of OC function, including multinuclearity, fusion, and resorption.
- Understanding how ncRNA-modulated OCs influence OB behavior is essential for deciphering bone remodeling communication.
Purpose of the Study:
- To investigate the impact of ncRNA-modified osteoclasts (OCs) on osteoblast (OB) lineage cells in a biomimetic co-culture system.
- To explore how ncRNAs (DLEU1 and miR-16) influence the secretome composition and resorption cavity remodeling by OCs.
- To assess the effects of ncRNA-engineered OCs on OB migratory capacity, morphology, and persistence.
Main Methods:
- Utilized a biomimetic co-culture system of human primary osteoblasts (OBs) and osteoclasts (OCs) without FBS or exogenous RANKL.
- Manipulated ncRNA levels in OCs: DLEU1 knockdown (siDLEU1-OCs) and miR-16 overexpression (miR-16-OCs).
- Analyzed changes in secreted factors, OB behavior (migration, morphology, ALP activity), and bone resorption cavity characteristics.
Main Results:
- siDLEU1-OCs altered OB secretomes, increasing RANKL, leptin, osteocalcin, MMP7, MMP8, TIMP1, and TIMP2.
- miR-16-OCs increased leptin and MMP8 levels in the co-culture.
- OBs co-cultured with siDLEU1-OCs showed impaired migration and increased ALP; OBs with miR-16-OCs showed reduced elongation. OBs persisted longer in siDLEU1-OC trenches.
- Silencing DLEU1 reduced individual trench area; miR-16 overexpression inhibited total eroded surface and trench formation.
Conclusions:
- DLEU1 and miR-16 are key regulators in the interplay between human primary OBs and OCs.
- ncRNAs within OCs modulate their paracrine and matrix-mediated effects on OBs.
- Targeting ncRNAs in OCs presents a potential strategy for modulating bone remodeling and treating bone disorders.
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