Related Experiment Video

Updated: Aug 29, 2026

A Pre-Clinical Model of Synovitis Using Ex vivo Human Synovial Tissue with Preserved Function and Architecture
08:32

A Pre-Clinical Model of Synovitis Using Ex vivo Human Synovial Tissue with Preserved Function and Architecture

Published on: March 20, 2026

JNK/SAPK is required in nitric oxide-induced apoptosis in osteoblasts

Young-Jin Kang1, Soo-Wan Chae

  • 1Department of Pharmacology, Institute of Cardiovascular Research, Chonbuk National University Medical School, Korea.

Archives of Pharmacal Research
|December 10, 2003
PubMed

Insights

Nitric oxide (NO) triggers apoptosis in human osteoblasts via the JNK/SAPK pathway. Inhibiting JNK significantly reduced NO-induced cell death, implicating this pathway in osteoblast apoptosis.

Area of Science:

  • Cell Biology
  • Biochemistry
  • Molecular Biology

Background:

  • Nitric oxide (NO) plays complex roles in cellular processes.
  • Osteoblasts are crucial for bone health and remodeling.
  • Understanding cell death mechanisms in osteoblasts is vital for bone disease research.

Purpose of the Study:

  • To investigate the role of nitric oxide (NO) in inducing apoptosis in human osteoblasts (MG-63 cell line).
  • To elucidate the signaling pathways involved in NO-induced osteoblast apoptosis.

Main Methods:

  • MG-63 osteoblasts were treated with exogenous NO donors (SNAP, SNP).
  • Apoptosis was assessed via morphological changes (Hoechst 33258 staining) and caspase activity assays.
  • Involvement of JNK, MEK, and p38 MAPK pathways was examined using specific inhibitors (Z-VAD-FMK, Ac-DEVD-CHO, PD98059, SB203580).

Main Results:

  • NO donors induced characteristic apoptotic morphological changes in osteoblasts.
  • NO-induced cell death involved increased activity of caspase-9 and caspase-3-like proteases.
  • The JNK/SAPK pathway was markedly activated by NO, and its inhibition reduced NO-induced apoptosis.
  • Inhibition of MEK (PD98059) or p38 MAPK (SB203580) did not affect NO-induced cell death.

Conclusions:

  • Nitric oxide induces apoptosis in human osteoblasts through caspase-dependent mechanisms.
  • The JNK/SAPK signaling pathway is critically involved in NO-induced osteoblast apoptosis.
  • Targeting the JNK pathway may offer therapeutic strategies for conditions involving aberrant osteoblast apoptosis.

Related Concept Videos

NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
NF-kB-dependent Signaling Pathway02:26

NF-kB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
Apoptosis01:30

Apoptosis

Apoptosis is a combination of two Greek words, 'apo' and 'ptosis,' meaning separation and falling off, respectively. Hippocrates used this word to describe gangrene, which was caused due to bandaging of fractured bones. Apoptosis was distinguished from necrosis in 1970 when John Kerr reported observations of morphological changes occurring during apoptosis. During one experiment, he observed that the disruption of blood supply to the liver tissue resulted in a size reduction of the tissue.
The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...