Selective β2-adrenoreceptor signaling regulates osteoclastogenesis via modulating RANKL production and neuropeptides

Hengxing Liang1, Yuanyuan Zeng2, Yunzhi Feng2

  • 1Department of Thoracic Surgery, The Second Xiangya Hospital, Central South University, Changsha, China.

Insights

Stimulating beta2-adrenergic receptors (β2-AR) in osteocytes influences bone turnover by modulating RANKL/OPG and neuropeptides. This suggests β2-AR signaling is a potential therapeutic target for bone diseases.

Area of Science:

  • Bone Biology and Endocrinology
  • Cellular and Molecular Medicine

Background:

  • Sympathetic nervous system influences bone turnover primarily through beta2-adrenergic receptor (β2-AR) signaling on bone cells.
  • The precise mechanisms involving receptor activator of nuclear factor κ-Β ligand (RANKL) modulation and neuropeptide expression in osteocytes remain largely unelucidated.

Purpose of the Study:

  • To investigate the role of β2-AR stimulation in osteocytic MLO-Y4 cells.
  • To examine the effects on cell cycle, proliferation, RANKL and osteoprotegerin (OPG) expression, and neuropeptide regulation.

Main Methods:

  • Osteocytic MLO-Y4 cells were treated with clenbuterol (CLE), a β2-AR agonist, and a β2-AR blocker.
  • Cell cycle analysis, proliferation assays, gene and protein expression analysis of RANKL and OPG were performed.
  • Co-culture systems with RAW264.7 cells were used to assess osteoclast formation and bone resorption.

Main Results:

  • CLE promoted MLO-Y4 cell growth and increased S-phase fraction, but did not affect the proliferation index.
  • CLE enhanced osteoclast formation, bone resorption, RANKL expression, and the RANKL/OPG ratio in osteocytes.
  • CLE inhibited neuropeptide Y and α-calcitonin gene-related peptide expression, effects reversed by β2-AR blockade.

Conclusions:

  • Osteocytic β2-AR signaling plays a significant role in regulating RANKL/OPG balance and neuropeptide expression.
  • β2-AR signaling in osteocytes represents a potential therapeutic target for managing osteoclast-related bone diseases.

Related Concept Videos

Regulation of Expression Occurs at Multiple Steps02:24

Regulation of Expression Occurs at Multiple Steps

Gene expression can be regulated at almost every step from gene to protein. Transcription is the step that is most commonly regulated. This involves the binding of proteins to short regulatory sequences on the DNA. This association can either promote or inhibit the transcription of a gene associated with the respective sequence.
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...
26.4K
Regulation of Expression Occurs at Multiple Steps02:24

Regulation of Expression Occurs at Multiple Steps

4.0K
What is Cell Signaling?02:03

What is Cell Signaling?

Despite the protective membrane that separates a cell from the environment, cells need the ability to detect and respond to environmental changes. Additionally, cells often need to communicate with one another. Unicellular and multicellular organisms use a variety of cell signaling mechanisms to communicate to respond to the environment.
130.4K
Cell Specific Gene Expression01:58

Cell Specific Gene Expression

Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
16.5K
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...
1.4K
Bacterial Signaling01:30

Bacterial Signaling

Bacterial signaling can occur within bacteria (intracellular) or between bacteria (intercellular). At times, a group of bacteria behaves like a community. To achieve this, they engage in quorum sensing, the perception of higher cell density that causes changes in gene expression. Quorum sensing involves both extracellular and intracellular signaling. The signaling cascade starts with a molecule called an autoinducer (AI). Individual bacteria produce AIs that move out of the bacterial cell...
40.7K