2. Academic Validation
  3. USP7 inhibitor HBX41108 suppresses osteoblastic differentiation in vitro and disrupts osseointegration of dental implants in vivo

USP7 inhibitor HBX41108 suppresses osteoblastic differentiation in vitro and disrupts osseointegration of dental implants in vivo

  • Toxicol Appl Pharmacol. 2025 Oct 9:505:117593. doi: 10.1016/j.taap.2025.117593.
Xiaofei Dong 1,  Enkang Tong 1,  Cuicui Zhao 1,  Yuan Sui 1,  Rongrong Nie 2,  Xiaodong Han 3,  Xiangfeng Meng 4
Affiliations

Affiliations

  • 1 Department of Prosthodontics, Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Institute of Stomatology, Nanjing University, Nanjing, Jiangsu 210008, PR China.
  • 2 Department of Geriatric Dentistry, Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Institute of Stomatology, Nanjing University, Nanjing, Jiangsu 210008, PR China.
  • 3 State Key Laboratory of Analytical Chemistry for Life Science & Jiangsu Key Laboratory of Molecular Medicine, Division of Anatomy and Histo-embryology, Medical School, Nanjing University, Nanjing, Jiangsu 210093, PR China.
  • 4 Department of Prosthodontic Technology, Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Institute of Stomatology, Nanjing University, Nanjing, Jiangsu 210008, PR China. Electronic address: mengsoar@nju.edu.cn.
PMID: 41067506 DOI: 10.1016/j.taap.2025.117593
Abstract

Objective: The purpose of this study was to investigate the effect of Ubiquitin-Specific Protease 7 (USP7) inhibitor HBX41108 on osteoblast proliferation and osteogenic differentiation in vitro, and implant osseointegration in vivo.

Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) and immunofluorescence staining were used to detect the expression of USP7 after osteogenic induction in MC3T3-E1 cells. USP7 Inhibitor HBX41108 was supplemented to induced mediums to observe cell proliferation by the CCK-8 assay, and osteogenic differentiation by Alkaline Phosphatase staining and qRT-PCR. HBX41108 was intraperitoneally administered for 4 weeks to rats inserted with titanium implants in the femoral metaphysis. Samples were observed by the histological staining and micro-computed tomography. The Wnt/β-catenin signaling pathway activator MBOC was added to verify the signaling pathway.

Results: USP7 markedly increased after osteogenic induction. USP7 Inhibitor HBX41108 suppressed cell proliferation and osteogenic differentiation. Moreover, HBX41108 hindered new bone formation around the implants in vivo. HBX41108 decreased the expression of phospho-β-catenin. MBOC reversed the decreased cell proliferation and osteogenic differentiation caused by HBX41108.

Conclusion: This study demonstrated that USP7 Inhibitor HBX41108 inhibited osteoblast proliferation and osteogenic differentiation in vitro via the Wnt/β-catenin signaling pathway, and hindered osseointegration of dental implants in vivo.

Keywords

HBX41108; Implant osseointegration; Osteoblastic differentiation; USP7; β-catenin.

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