Table 2 Relationship between TRPV5 and OP at different bone tissue levels

TRPV5

Bone Phenotype

In TRPV5^-/-mice, bone resorption is disordered and the thickness of the femur is decreased

The absence of TRPV5 results in accelerated bone aging and disturbance of bone resorption

[18, 117]

Bone Tissue Cells

In TRPV5^-/-mice, the number and size of osteoclast nuclei are significantly higher than those in WT mice; however, the absorptive capacity of osteoclasts is severely impaired

TRPV5 plays a crucial role in calcium transport within the resorption cavity of osteoclasts

E₂ can enhance the expression of TRPV5 and stimulate osteoclast apoptosis

[18, 121, 123, 164]

pH

External H⁺ influences the biological activity of TRPV5 by changing the conformation of TRPV5

“kiss and linger” way to affect TRPV5 activity

[73, 135]

Molecular mechanism

Binds to CaR and CaM proteins to regulate Ca²⁺ concentration. Several post-translational modifications (PTMs) play a role in modulating the activity of TRPV5:

• Phosphorylation-The cAMP-PKA pathway promotes the influx of Ca²⁺

• Glycosylation-vitamin D can upregulate Klotho and TRPV5, thereby regulating calcium concentrations in the blood

• Ubiquitination- through the E 1 to 3, Nedd 4–2, TRPV5 protein function is adjusted

[11, 74, 143, 151]

Activation and inhibition

PTH, VD₃, CaR, Klotho, PI(4,5)P₂, and others are common TRPV5 agonists that activate the channel’s activity and influence bone metabolism

In osteoclasts, econazole inhibits the expression of TRPV5 in a dose-dependent manner, and it can suppress bone resorption by OCs in rats

Oxoglaucine primarily obstructs the calmodulin transport pathway of TRPV 5 and suppresses Ca²⁺ influx, thereby inhibiting TRPV5 activity and promoting chondrocyte autophagy

Plasmin can influence the binding of calmodulin to TRPV5 and reduce the activity of the TRPV5 channel

[121, 152, 162, 163]