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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...
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Receptor tyrosine kinases or RTKs are membrane-bound receptors that phosphorylate specific tyrosine on protein substrates. RTKs regulate cellular growth, differentiation, survival, and migration. They contain an extracellular ligand binding domain, a transmembrane domain, and a cytosolic tail with intrinsic kinase activity. Several extracellular signaling molecules activate RTKs in one or more ways and relay the signal downstream. Ligands such as platelet-derived growth factor (PDGF) or...
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Drugs target macromolecules to modify ongoing cellular processes. Primary drug targets include receptors, ion channels, transporters, and enzymes.
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Related Experiment Video

Updated: Jul 6, 2025

A RANKL-based Osteoclast Culture Assay of Mouse Bone Marrow to Investigate the Role of mTORC1 in Osteoclast Formation
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Is RANKL a potential molecular target in osteoarthritis?

Dzenita Muratovic1, Gerald J Atkins1, David M Findlay2

  • 1Centre for Orthopaedic & Trauma Research, The University of Adelaide, Adelaide, South Australia 5000, Australia; Biomedical Orthopaedic Research Group, Centre for Orthopaedic & Trauma Research, The University of Adelaide, Adelaide, South Australia 5000, Australia.

Osteoarthritis and Cartilage
|December 31, 2023
PubMed
Summary

Osteoarthritis involves increased bone remodeling under cartilage. Understanding subchondral bone changes and targeting Receptor Activator of NFκB ligand (RANKL) may lead to new osteoarthritis treatments.

Keywords:
Bone remodellingOPG/RANK/RANKLOsteoarthritis

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Area of Science:

  • Orthopedics
  • Rheumatology
  • Cell Biology

Background:

  • Osteoarthritis (OA) is a joint disease characterized by increased bone remodeling in the subchondral bone (SCB).
  • SCB remodeling significantly alters joint biomechanics and plays a crucial role in OA initiation and progression.

Purpose of the Study:

  • To review the current understanding of OA etiology, focusing on SCB events, cells, and cytokines.
  • To explore the potential of targeting bone remodeling mechanisms for disease-modifying OA treatments.

Main Methods:

  • Systematic review of existing literature on OA pathogenesis.
  • Emphasis on cellular and molecular mechanisms within the subchondral bone.

Main Results:

  • SCB remodeling alters joint microstructure and load-bearing properties, contributing to OA.
  • Receptor Activator of NFκB ligand (RANKL) and osteoprotegerin are key regulators of bone remodeling relevant to OA.
  • The precise role of RANKL in OA pathogenesis and the efficacy of its neutralization require further investigation.

Conclusions:

  • Subchondral bone remodeling is a critical factor in osteoarthritis.
  • Further research into the pathophysiological role of RANKL in OA is warranted.
  • RANKL presents a potential therapeutic target for osteoarthritis.