Related Experiment Video
Updated: Oct 31, 2025

In Vivo Inhibition of MicroRNA to Decrease Tumor Growth in Mice
Published on: August 23, 2019
Inhibition of miR-29 Activity in the Myeloid Lineage Increases Response to Calcitonin and Trabecular Bone Volume in
Bongjin Shin1,2, Henry C Hrdlicka3, Anne M Delany3
1Center on Aging, UConn Health, Farmington, CT 06030, USA.
Abstract:
The miR-29-3p family (miR-29a, miR-29b, miR-29c) of microRNAs is increased during receptor activator of nuclear factor kappa-B ligand (RANKL)-induced osteoclastogenesis. In vivo, activation of a miR-29-3p tough decoy inhibitor in Cre recombinase under the control of the lysozyme 2 promoter-expressing cells (myeloid lineage) resulted in mice displaying enhanced trabecular and cortical bone volume because of decreased bone resorption. Calcitonin receptor (Calcr) is a miR-29 target that negatively regulates bone resorption. CALCR was significantly increased in RANKL-treated miR-29-decoy osteoclasts, and these cells were more responsive to the inhibitory effect of calcitonin on osteoclast formation. Further, cathepsin K (Ctsk), which is critical for resorption, was decreased in miR-29-decoy cells. CALCR is a Gs-coupled receptor and its activation raises cAMP levels. In turn, cAMP suppresses cathepsin K, and cAMP levels were increased in miR-29-decoy cells. siRNA-mediated knock-down of Calcr in miR-29 decoy osteoclasts allowed recovery of cathepsin K levels in these cells. Overall, using a novel knockin tough decoy mouse model, we identified a new role for miR-29-3p in bone homeostasis. In RANKL-driven osteoclastogenesis, as seen in normal bone remodeling, miR-29-3p promotes resorption. Consequently, inhibition of miR-29-3p activity in the myeloid lineage leads to increased trabecular and cortical bone. Further, this study documents an interrelationship between CALCR and CTSK in osteoclastic bone resorption, which is modulated by miR-29-3p.
Insights
Inhibition of miR-29-3p microRNAs in myeloid cells enhances bone volume by reducing bone resorption. This study reveals miR-29-3p
Area of Science:
- Molecular Biology
- Bone Biology
- MicroRNA Therapeutics
Background:
- MicroRNAs (miRNAs) regulate cellular processes, including bone metabolism.
- The miR-29-3p family is implicated in osteoclastogenesis, the process of bone resorption.
- Understanding miRNA roles is crucial for developing bone disease treatments.
Purpose of the Study:
- To investigate the role of miR-29-3p in bone homeostasis and osteoclast function.
- To explore the therapeutic potential of inhibiting miR-29-3p in vivo.
- To elucidate the molecular mechanisms linking miR-29-3p to bone resorption.
Main Methods:
- Development of a novel knockin tough decoy mouse model to inhibit miR-29-3p in myeloid cells.
- Analysis of bone volume (trabecular and cortical) and bone resorption markers in vivo.
- In vitro studies using osteoclasts to assess the impact of miR-29-3p inhibition on calcitonin receptor (Calcr) and cathepsin K (Ctsk) expression and function.
Main Results:
- Inhibition of miR-29-3p in myeloid lineage cells led to increased trabecular and cortical bone volume due to decreased bone resorption.
- miR-29-3p inhibition upregulated Calcitonin receptor (Calcr) expression, enhancing osteoclast responsiveness to calcitonin.
- Cathepsin K (Ctsk) levels were decreased in miR-29-3p inhibited osteoclasts, with Calcr knockdown restoring Ctsk levels, indicating a Calcr-cAMP-Ctsk pathway modulated by miR-29-3p.
Conclusions:
- miR-29-3p promotes bone resorption during RANKL-induced osteoclastogenesis and normal bone remodeling.
- Inhibiting miR-29-3p in the myeloid lineage offers a potential therapeutic strategy for increasing bone mass.
- This study establishes a novel link between miR-29-3p, Calcr, and Ctsk in regulating osteoclastic bone resorption and bone homeostasis.
More Related Videos
06:59Author Spotlight: An Economic and Efficient Method for Quantitative Evaluation of Bone Microarchitecture in a Murine Osteoporosis Model
Published on: September 8, 2023
09:37A RANKL-based Osteoclast Culture Assay of Mouse Bone Marrow to Investigate the Role of mTORC1 in Osteoclast Formation
Published on: March 15, 2018
Related Concept Videos
Hormones and Bone Tissue
Hormones That Influence Osteoblasts and/or Maintain the Matrix
Several hormones are necessary for controlling bone growth and maintaining the bone matrix. The pituitary gland secretes growth hormone (GH), which, as its name implies, controls bone growth. This happens in several ways: first, it triggers chondrocyte...
Synthesis and Functions of Calcitonin
The exact mechanisms by which calcitonin operates in calcium homeostasis remain elusive, but its significance is evident in several vital...
Osteoclasts in Bone Remodeling
Skeleton and Calcium Homeostasis
Bone Remodeling