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Osteoclastogenesis inhibitory factor (OCIF) directly inhibits bone-resorbing activity of isolated mature osteoclasts
Y Hakeda1, Y Kobayashi, K Yamaguchi
1Department of Oral Anatomy, Meikai University School of Dentistry, Saitama, Sakado, 350-0283, Japan. y-hakeda@dent.meikai.ac.jp
Abstract:
Osteoclastogenesis inhibitory factor (OCIF) was previously reported to specifically inhibit osteoclast development by interrupting the action of osteoclast differentiation factor (ODF), which is expressed in stromal cells and plays an important role in osteoclastogenesis. Here we report the direct action of OCIF on isolated rabbit mature osteoclasts to inhibit their functional bone-resorbing activity. The cell population employed in this study consisted of mature osteoclasts with more than 95% of purity. The inhibition by OCIF was dose dependent and observed as early as 6 h after the OCIF addition. An OCIF-binding protein of 140 kDa was detected on the plasma membrane of osteoclasts. ODF with a Mr of 40 kDa was recently isolated as a ligand for OCIF and shows to be identical to TRANCE/RANKL. However, ODF was not detected in osteoclasts. OCIF did not have any impact on the mRNA levels of cathepsin K/OC2 and carbonic anhydrase II responsible for degradation of organic and inorganic bone matrices, respectively, or on osteoclast apoptosis. However, OCIF reduced or disrupted the formation of F-actin ring in isolated osteoclasts, the cytoskeletal structure of which is correlated with bone resorption. These findings demonstrate that OCIF directly inhibits osteoclast function through an ODF-independent mechanism besides blocking the generation of osteoclasts.
Insights
Osteoclastogenesis inhibitory factor (OCIF) directly inhibits mature osteoclast bone-resorbing activity by disrupting actin ring formation, independent of osteoclast differentiation factor (ODF). This reveals a novel mechanism for OCIF in regulating bone metabolism.
Area of Science:
- Bone Biology
- Cellular Physiology
- Biochemistry
Background:
- Osteoclastogenesis inhibitory factor (OCIF) is known to inhibit osteoclast development.
- This inhibition was thought to occur by interrupting osteoclast differentiation factor (ODF).
- ODF plays a crucial role in osteoclastogenesis.
Purpose of the Study:
- To investigate the direct effect of OCIF on mature osteoclast bone-resorbing activity.
- To elucidate the mechanism of OCIF's action on osteoclasts.
Main Methods:
- Isolated mature rabbit osteoclasts (purity >95%) were treated with OCIF.
- OCIF's effect on bone resorption, F-actin ring formation, and mRNA levels of bone-degrading enzymes was assessed.
- OCIF-binding proteins on osteoclast membranes were identified.
Main Results:
- OCIF directly inhibited osteoclast bone-resorbing activity in a dose-dependent manner.
- OCIF disrupted the formation of F-actin rings, crucial for bone resorption.
- No impact on cathepsin K/OC2 or carbonic anhydrase II mRNA levels or osteoclast apoptosis was observed.
- An OCIF-binding protein (140 kDa) was detected on osteoclast plasma membranes.
Conclusions:
- OCIF directly inhibits mature osteoclast function through an ODF-independent mechanism.
- OCIF disrupts osteoclast cytoskeletal structure (F-actin ring), impacting bone resorption.
- This study reveals a novel direct inhibitory role of OCIF on osteoclast activity beyond blocking osteoclast generation.