Effects of ADRM1 on osteoblast differentiation and mineralization in osteoporosis.

Objective: Adhesion regulating molecule-1 (ADRM1), a 26S proteasome adaptor protein, plays a crucial role in mediating the growth and differentiation of osteoclasts in osteoporosis (OP). However, its involvement in this osteoanabolic effect remains largely uninvestigated.

Methods: In vitro experiments, including both gain-of-function and loss-of-function approaches, were conducted in MC3T3-E1 and C3H10T1/2 cells.

Results: Knockdown of ADRM1 markedly promoted the growth of C3H10T1/2 cells while inhibiting apoptosis. Additionally, this intervention enhanced the expression of osteoblast differentiation markers and key proteins associated with the Wnt/β-catenin pathway. Notably, silencing ADRM1 promoted osteoblast mineralization and differentiation, as evidenced by increased Alizarin red staining and alkaline phosphatase staining. Conversely, MC3T3-E1 cells overexpressing ADRM1 exhibited results that were diametrically opposed to those observed with ADRM1 knockdown. Furthermore, treatment with ICG-001 (a Wnt/β-catenin pathway antagonist) reversed the effects of ADRM1 knockdown in C3H10T1/2 cells.

Conclusions: Our findings suggest that silencing ADRM1 induces osteoblast mineralization and differentiation by activating the Wnt/β-catenin pathway. This finding underscores the therapeutic potential of the ADRM1/Wnt/β-catenin axis in treating OP.