Related Experiment Videos

Epigenetic modulation of the JAK2-STAT3 signaling pathway in osteoporosis: non-coding RNA networks as therapeutic

Pengjun Wang1, Lu Xia1, Xiaobin Shang2

  • 1Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan, China.

Journal of Translational Medicine
|July 16, 2026
PubMed
Abstract

Insights

Non-coding RNAs (ncRNAs) precisely regulate the JAK2-STAT3 pathway, offering a novel therapeutic target for osteoporosis. Targeting this ncRNA network can restore bone homeostasis and advance precision medicine for metabolic bone diseases.

Area of Science:

  • Molecular Biology
  • Genetics
  • Biochemistry

Background:

  • Osteoporosis affects over 200 million people globally, characterized by bone resorption/formation imbalance and increased fracture risk.
  • Chronic activation of the Janus kinase 2-signal transducer and activator of transcription 3 (JAK2-STAT3) pathway dysregulates bone metabolism in osteoporosis.
  • Understanding JAK2-STAT3 pathway regulation is crucial for developing effective osteoporosis therapies.

Purpose of the Study:

  • To review the role of non-coding RNAs (ncRNAs) in regulating the JAK2-STAT3 signaling pathway.
  • To explore the therapeutic potential of targeting ncRNAs for osteoporosis and metabolic bone diseases.

Main Methods:

  • Review of scientific literature on ncRNAs, JAK2-STAT3 pathway, and bone metabolism.
  • Analysis of miRNA, lncRNA, and circRNA interactions within the JAK2-STAT3 regulatory network.
  • Examination of ncRNA influence on osteoblast and osteoclast activity, osteogenic differentiation, and inflammatory responses.

Main Results:

  • Specific microRNAs (miRNAs) directly target JAK2-STAT3 pathway components, modulating osteoblast and osteoclast activity.
  • Long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) function as competitive endogenous RNAs (ceRNAs), indirectly regulating JAK2-STAT3 signaling.
  • The ncRNA network impacts osteogenic differentiation, inflammation, and mitochondrial redox homeostasis, influencing overall bone metabolic balance.

Conclusions:

  • The ncRNA network offers a promising therapeutic target for osteoporosis and metabolic diseases by precisely controlling the JAK2-STAT3 pathway.
  • Targeting ncRNAs via advanced delivery systems like engineered exosomes or biomaterials presents a novel strategy for bone homeostasis restoration.
  • This approach paves the way for precision medicine in managing bone metabolic diseases.
Keywords:
Bone metabolismEpigenetic regulationJAK2-STAT3 signalingNon-coding RNAsOsteoporosismicroRNAs

Related Concept Videos

The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...
Regulation of Expression at Multiple Steps01:23

Regulation of Expression at Multiple Steps

The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the addition of a...
What is Gene Expression?01:36

What is Gene Expression?

A gene is a stretch of DNA that serves as the blueprint for functional RNAs and proteins. Since DNA is comprised  of nucleotides and proteins are comprised of amino acids, a mediator is required to convert the information encoded in DNA into proteins. This mediator is the messenger RNA (mRNA). mRNA copies the blueprint from DNA by a process called transcription. In eukaryotes, transcription occurs in the nucleus by complementary base-pairing with the DNA template. The mRNA is then processed and...
Epigenetic Regulation01:37

Epigenetic Regulation

Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...
Epigenetic Regulation01:46

Epigenetic Regulation

Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.