Deubiquitinating Enzymes and Bone Remodeling

Table 2

Deubiquitinases and bone remodeling.

Family	Name	Function	Mechanism	Ref.
USP	USP4	Inhibits osteoblast differentiation and mineralization	Regulates Wnt signaling by deubiquitinating Dvl, Nik, TGF4, and β-catenin; may regulate TGF/BMP signal	[67–79, 81–85]
	USP7	Enhances osteogenic differentiation of hASCs	Stabilizes PHF8 that triggers osteogenic differentiation of BMMSCs	[69, 86–88]
	USP15	Enhances osteoblast-mediated bone formation	Regulates Wnt signaling via deubiquitinating β-catenin	[67, 89–92]
	CYLD	Inhibits osteoclastogenesis	Regulates RANK signaling through deubiquitinating TRAF6	[97–99]
	USP18	Inhibits osteoclastogenesis	Regulates IFN signaling by deconjugating ISGlation	[75, 102–104]
	USP15	Inhibits osteoclastogenesis	Stabilizes IκBα, leading to decreased RANKL-mediated NF-κB activation	[74]
	USP2	Necessary for PTH (1-34) to induce osteoblast proliferation	Upregulated by the PKA/cAMP pathway and stabilizes PTHR	[105–108]
UCH	UCH-L3	Increases osteoblast differentiation	Interacts with Smad1 and stabilizes it by deubiquitylating its polyubiquitin	[71]
OTU	A20	Inhibits osteoclastogenesis	Regulates RANK signaling by controlling TRAF6 and NF-κB degradation	[76, 119–123]
JAMM	POH1	Enhances osteoclast differentiation	Regulates Mitf	[126]
	MYSM1	Enhances osteogenic differentiation	—	[73, 127, 128]