Related Experiment Video

Updated: Jun 18, 2026

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

PDE4 inhibitor upregulates PTH-induced osteoclast formation via CRE-mediated COX-2 expression in osteoblasts

Hyojung Park1, A Long Sae Mi No, Jung-Min Lee

  • 1College of Pharmacy, Sookmyung Women's University, Seoul, Republic of Korea.

FEBS Letters
|November 21, 2009
PubMed

Insights

A phosphodiesterase 4 (PDE4) inhibitor enhances parathyroid hormone (PTH)-induced osteoclast formation. This effect is partly mediated by cyclooxygenase-2 (COX-2) mRNA expression via cAMP-response element (CRE) signaling.

Area of Science:

  • Molecular Endocrinology
  • Bone Biology
  • Cell Signaling

Background:

  • Parathyroid hormone (PTH) is a key regulator of bone metabolism.
  • Phosphodiesterases (PDEs) modulate intracellular signaling pathways, including those influenced by PTH.
  • Osteoblasts play a crucial role in bone remodeling and are targets of PTH action.

Purpose of the Study:

  • To elucidate the role of phosphodiesterase 4 (PDE4) in mediating parathyroid hormone (PTH) effects on osteoblasts.
  • To investigate the molecular mechanisms linking PDE4 inhibition, PTH signaling, and osteoclastogenesis.
  • To determine the involvement of cyclooxygenase-2 (COX-2) and cAMP-response element (CRE) in these processes.

Main Methods:

  • Treatment of osteoblasts with PTH and a PDE4 inhibitor.
  • Measurement of intracellular cAMP levels.
  • Analysis of osteoclast formation and RANKL mRNA expression.
  • Assessment of COX-2 mRNA expression and its regulation by CREB and CRE sites.

Main Results:

  • PDE4 was found to negatively regulate PTH-induced cAMP accumulation in osteoblasts.
  • Inhibition of PDE4 enhanced PTH-induced osteoclast formation and RANKL mRNA expression.
  • This enhancement was partially mediated by COX-2 mRNA expression, dependent on CRE sites and CREB activation.

Conclusions:

  • PDE4 inhibition promotes PTH-induced osteoclast formation in osteoblasts.
  • The mechanism involves enhanced COX-2 mRNA expression through a pathway dependent on CRE sites and CREB activation.
  • These findings highlight a novel signaling axis involving PDE4, PTH, CREB, COX-2, and osteoclastogenesis.

Related Concept Videos

Hormones and Bone Tissue01:17

Hormones and Bone Tissue

The endocrine system produces and secretes hormones, which interact with the skeletal system. These hormones control bone growth, maintain bone once it is formed, and remodel it.
Hormones That Influence Osteoblasts and/or Maintain the Matrix
Several hormones are necessary for controlling bone growth and maintaining the bone matrix. The pituitary gland secretes growth hormone (GH), which, as its name implies, controls bone growth. This happens in several ways: first, it triggers chondrocyte...
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 bone...
Bone Remodeling01:40

Bone Remodeling

Bone remodeling is a continuous and balanced process of bone resorption by osteoclasts and bone formation by osteoblasts. In adults, it helps maintain bone mass and calcium homeostasis. While mechanical stress can stimulate turnover as part of the normal maintenance and reparative process, several hormones also regulate bone remodeling.
The Parathyroid Glands00:59

The Parathyroid Glands

The two pairs of parathyroid glands embedded within the posterior surface of the thyroid gland are restricted by a dense capsule around them. These glands comprise two distinct cell populations—parathyroid oxyphil and parathyroid principal cells- pivotal in calcium homeostasis.
Oxyphil cells, whose functions remain elusive, emerge during late puberty, adding a layer of complexity to the parathyroid gland's intricacies. In contrast, principal parathyroid cells undertake a vital role by producing...
GPCRs Regulate Adenylyl Cylase Activity01:09

GPCRs Regulate Adenylyl Cylase Activity

Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of cells.
Two...
Antiplatelet Drugs: Prostaglandin Synthesis, P2Y12 and Glycoprotein IIb/IIIa Inhibitors01:20

Antiplatelet Drugs: Prostaglandin Synthesis, P2Y12 and Glycoprotein IIb/IIIa Inhibitors

Antiplatelet drugs emerge as frontline defenders against the insidious threat of thromboembolic diseases, where abnormal clots obstruct vital blood vessels. These drugs stand as bulwarks, inhibiting platelet aggregation and clot formation, thereby mitigating the risk of life-threatening conditions like myocardial infarction, coronary artery disease, and thrombotic strokes.
Prostaglandin synthesis inhibitors, exemplified by the widely known aspirin, wield their power by irreversibly acetylating...