Knockout of TRPV6 causes osteopenia in mice by increasing osteoclastic differentiation and activity.

Abstract

BACKGROUND:

Calcium ion (Ca(2+)) signals are required for osteoclast differentiation. Previous study showed that transient receptor potential vanilloid 5 (TRPV5) is an essential Ca(2+) transporter in osteoclastogenesis and bone resorption. TRPV5 and TRPV6 represent two highly homologous members within the transient receptor potential (TRP) superfamily. However, the role of TRPV6 in bone metabolism is still controversial and little is known about the involvement of TRPV6 in receptor activator of nuclear factor κ-B ligand (RANKL)-induced osteoclastogenesis.

METHODS:

In our study, gene knockout mice, RNA interference, western blot, quantitative real-time PCR, tartrate-resistant acid phosphatase (TRAP) staining, pit formation assay, histomorphometry and measurement of serum parameters were employed to investigate the role of TRPV6 in bone homeostasis, osteoclastogenesis and bone resorption.

RESULTS:

We found that TRPV6 depletion results in noticeable destruction of bone microarchitecture in TRPV6 knockout mice (TRPV6(-/-)), suggesting that TRPV6 is a critical regulator in bone homeostasis. Inactivation of Trpv6 had no effect on osteoblastic bone formation. However, quantification of the TRAP staining showed a significantly increased osteoclast number and surface area in the metaphyseal area of femurs bone sections derived from TRPV6(-/-) mice. In agreement with our observations from TRPV6(-/-) mice, TRPV6 depletion in vitro significantly increased osteoclasts differentiation and bone resorption activity.

CONCLUSION:

Based on these results above, we can draw conclusions that TRPV6 plays an essential role in bone metabolism and is a critical regulator in osteoclasts differentiation and bone resorption.

• Authors: Fangjing Chen, Bin Ni, Yueping Ou Yang, Tianwen Ye, Aimin Chen
• Journal: Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology (Cell Physiol Biochem) Vol. 33 Issue 3 Pg. 796-809 ( 2014) ISSN: 1421-9778 [Electronic] Germany
• PMID: 24686448 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 S. Karger AG, Basel.

Chemical References

• Calcium Channels
• Isoenzymes
• RANK Ligand
• TRPV Cation Channels
• Tnfsf11 protein, mouse
• Trpv6 protein, mouse
• Acid Phosphatase
• Acp5 protein, mouse
• Tartrate-Resistant Acid Phosphatase

Topics

• Acid Phosphatase (genetics, metabolism)
• Animals
• Bone Diseases, Metabolic (genetics, metabolism, pathology)
• Calcium Channels (deficiency)
• Calcium Signaling
• Cell Differentiation
• Femur (metabolism, pathology)
• Isoenzymes (genetics, metabolism)
• Mice
• Mice, Knockout
• Osteoclasts (metabolism, pathology)
• RANK Ligand (genetics, metabolism)
• TRPV Cation Channels (deficiency)
• Tartrate-Resistant Acid Phosphatase