Related Experiment Video
Updated: Aug 6, 2026
05:55
Tension-Free Weight-Bearing Model of Steroid-Induced Osteonecrosis of Femoral Head in Rats
Published on: September 27, 2024
Glucocorticoids suppress bone formation via the osteoclast
Hyun-Ju Kim1, Haibo Zhao, Hideki Kitaura
1Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
The Journal of Clinical Investigation
|August 1, 2006
Summary
Glucocorticoids (GCs) cause bone loss by impairing osteoclast function, not directly harming osteoblasts. Osteoclasts mediate GC effects, impacting bone remodeling and formation.
Area of Science:
- Bone Biology
- Endocrinology
- Cell Biology
Background:
- Glucocorticoid (GC)-induced bone loss pathogenesis is unclear, with conflicting in vivo and in vitro effects on osteoblasts.
- Bone remodeling involves coupled osteoclast and osteoblast activity, suggesting intermediary cells may mediate GC effects.
Purpose of the Study:
- To investigate the direct impact of GCs on bone-resorptive cells (osteoclasts).
- To determine if osteoclasts mediate the bone-suppressive effects of GCs on osteoblasts.
Main Methods:
- Compared effects of dexamethasone (DEX) on wild-type (WT) osteoclasts and osteoclasts from mice lacking GC receptors in osteoclast lineage cells (GRoc-/-).
- Assessed osteoclast longevity, bone-degrading capacity, and cytoskeletal organization.
- Analyzed M-CSF activation of RhoA, Rac, and Vav3 signaling pathways.
Main Results:
- DEX prolonged osteoclast longevity but suppressed their bone-degrading capacity by disrupting cytoskeletal organization.
- DEX inhibited M-CSF activation of RhoA, Rac, and Vav3, crucial for osteoclast cytoskeleton.
- GRoc-/- mice were protected from DEX effects on osteoclasts and osteoblast suppression, indicating osteoclasts mediate GC-induced bone loss.
Conclusions:
- Osteoclasts mediate the bone-suppressive effects of GCs, rather than GCs directly inhibiting osteoblasts.
- Targeting osteoclast GC receptor signaling could prevent GC-induced bone loss.
Related Concept Videos
01:31Osteoclasts 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...
01:17Hormones 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...
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...
01:29Bone Disorders
Aging and its effect on bone remodeling is the most common cause of bone disorders. In young and healthy people, bone deposition and resorption happen at an equal rate to maintain optimal bone health.
Bone deposition is also affected by the levels of sex hormones like estrogen and testosterone that promote osteoblast activity and bone matrix synthesis. When the level of these hormones decreases due to aging, it causes a reduction in bone deposition. As a result, bone resorption by osteoclasts...
Bone deposition is also affected by the levels of sex hormones like estrogen and testosterone that promote osteoblast activity and bone matrix synthesis. When the level of these hormones decreases due to aging, it causes a reduction in bone deposition. As a result, bone resorption by osteoclasts...
01:40Bone 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.
01:21Drugs for Treatment of Crohn's Disease in IBD Using Glucocorticoids
Glucocorticoids, a class of anti-inflammatory drugs, are pivotal in treating moderate to severe Crohn's disease by inducing remission. They exhibit their anti-inflammatory action by inhibiting the production of inflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-1, and chemokines like IL-8. In addition, they reduce the expression of inflammatory cell adhesion molecules and inhibit gene transcription of nitric oxide synthase, phospholipase A2, cyclooxygenase-2 (COX-2),...
01:21Skeleton and Calcium Homeostasis
Calcium is not only the most abundant mineral in bone but also the most abundant mineral in the human body. Calcium ions are needed for bone mineralization, tooth health, heart rate regulation and strength of contraction, blood coagulation, the contraction of smooth and skeletal muscle cells, and the regulation of nerve impulse conduction. The average calcium level in the blood is about 10 mg/dL. When the body cannot maintain this level, a person will experience hypo or hypercalcemia.