Related Experiment Video

Updated: Sep 27, 2025

A Simple Pit Assay Protocol to Visualize and Quantify Osteoclastic Resorption In Vitro
07:03

A Simple Pit Assay Protocol to Visualize and Quantify Osteoclastic Resorption In Vitro

Published on: June 16, 2022

6.5K

7-Ketocholesterol-Induced Micro-RNA-107-5p Increases Number and Activity of Osteoclasts by Targeting MKP1

Guoen Li1, Ok-Joo Sul1, Rina Yu2

  • 1Department of Biological Sciences (BK21 Program), University of Ulsan, Ulsan 44610, Korea.

International Journal of Molecular Sciences
|April 12, 2022
PubMed

Insights

7-ketocholesterol (7-KC) increases microRNA-107-5p (miR-107-5p), which promotes osteoclast (OC) activity. This study reveals miR-107-5p as a key player in cholesterol-induced bone loss by downregulating MKP1.

Area of Science:

  • Bone Biology
  • Molecular Endocrinology
  • MicroRNA Therapeutics

Background:

  • Osteoclasts (OCs) mediate bone resorption and are implicated in cholesterol-induced bone loss.
  • MicroRNAs (miRs) are increasingly recognized for their role in modulating OC function.
  • 7-ketocholesterol (7-KC), a cholesterol metabolite, is linked to bone loss, but its molecular mechanisms involving miRs are not fully understood.

Purpose of the Study:

  • To investigate the role of miR-107-5p in 7-KC-induced osteoclastogenesis.
  • To elucidate the molecular mechanism by which miR-107-5p affects osteoclast differentiation and function.

Main Methods:

  • Osteoclast differentiation was induced using receptor activator of nuclear factor kappa-B ligand (RANKL).
  • miR-107-5p expression was manipulated using mimics and anti-miRs.
  • Osteoclast activity was assessed via tartrate-resistant alkaline phosphatase (TRAP) staining, qPCR, and Western blotting.
  • Target gene validation involved analyzing the 3'-untranslated region (3'-UTR) of potential candidates.

Main Results:

  • 7-KC exposure upregulated miR-107-5p in RANKL-stimulated osteoclasts.
  • miR-107-5p upregulation was also observed in tibiae of mice fed an atherogenic diet.
  • Overexpression of miR-107-5p enhanced OC differentiation and function, while inhibition had the opposite effect.
  • Mitogen-activated protein kinase phosphatase-1 (MKP1) was identified as a direct target gene of miR-107-5p.

Conclusions:

  • 7-KC induces miR-107-5p expression, promoting osteoclast differentiation and bone resorption.
  • The mechanism involves the downregulation of MKP1 by miR-107-5p.
  • miR-107-5p represents a potential therapeutic target for managing cholesterol-induced bone loss.
Keywords:
7-ketocholesterolmicro-RNA-107-5pmitogen-activated protein kinase phosphatase 1osteoclast

More Related Videos

A RANKL-based Osteoclast Culture Assay of Mouse Bone Marrow to Investigate the Role of mTORC1 in Osteoclast Formation09:37

A RANKL-based Osteoclast Culture Assay of Mouse Bone Marrow to Investigate the Role of mTORC1 in Osteoclast Formation

Published on: March 15, 2018

13.3K
A Novel in vivo Gene Transfer Technique and in vitro Cell Based Assays for the Study of Bone Loss in Musculoskeletal Disorders11:47

A Novel in vivo Gene Transfer Technique and in vitro Cell Based Assays for the Study of Bone Loss in Musculoskeletal Disorders

Published on: June 8, 2014

11.8K

Related Concept Videos

Osteoclasts in Bone Remodeling01:31

Osteoclasts in Bone Remodeling

Osteoclasts are cells responsible for bone resorption and remodeling. They originate from hematopoietic progenitor cells present in the bone marrow. Numerous progenitor cells fuse to form multinucleated cells, each with 10-20 nuclei. A single osteoclast has a diameter of 150 to 200 µM. These cells have ruffled borders that break down the underlying bone tissue and release minerals such as calcium into the blood in bone resorption. Osteoclasts cling to bones with their ruffled edges during...
3.3K
MicroRNAs01:22

MicroRNAs

MicroRNA (miRNA) are short, regulatory RNA transcribed from introns (non-coding regions of a gene) or intergenic regions (stretches of DNA present between genes). Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself, forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA...
3.1K
Cholesterol: Significance and Regulation01:29

Cholesterol: Significance and Regulation

Although not a source of energy, cholesterol plays a significant role as a foundational structure for bile salts, steroid hormones, and vitamin D, as well as being a crucial component of plasma membranes. Approximately 15% of blood cholesterol is derived from our diet, with the remainder synthesized from acetyl CoA by the liver and intestines. Cholesterol is eliminated from the body through its conversion into bile salts, which are eventually discarded in the feces.
Considering cholesterol and...
720