2. Academic Validation
  3. ADAM8 negatively regulates the osteogenic differentiation of rat tendon stem cells through inhibiting the PI3K/AKT signaling pathway

ADAM8 negatively regulates the osteogenic differentiation of rat tendon stem cells through inhibiting the PI3K/AKT signaling pathway

  • Exp Cell Res. 2026 Apr 1;457(1):114924. doi: 10.1016/j.yexcr.2026.114924.
Weiyu Jiang 1,  Zhehua Zhang 2,  Yan Liu 3
Affiliations

Affiliations

  • 1 Baotou Medical College, Inner Mongolia Autonomous Region, Baotou, 014040, PR China; Department of Orthopedics, Baogang Hospital of Inner Mongolia (The Third Affiliated Hospital of Inner Mongolia Medical University), Inner Mongolia Autonomous Region, Baotou, 014010, PR China.
  • 2 Department of Orthopedics, Baogang Hospital of Inner Mongolia (The Third Affiliated Hospital of Inner Mongolia Medical University), Inner Mongolia Autonomous Region, Baotou, 014010, PR China.
  • 3 Department of Orthopedics, Baogang Hospital of Inner Mongolia (The Third Affiliated Hospital of Inner Mongolia Medical University), Inner Mongolia Autonomous Region, Baotou, 014010, PR China; Department of Orthopedics, Xiongan Xuanwu Hospital, Xiongan New Area, 070001, Hebei Province, PR China. Electronic address: [email protected].
PMID: 41655939 DOI: 10.1016/j.yexcr.2026.114924
Abstract

Background: Tendon-bone healing refers to the repair process at the tendon-bone interface following injury, during which the osteogenic differentiation of tendon stem cells (TSCs) plays a critical role. The present research aims to elucidate the role of ADAM8 in regulating the osteogenic differentiation of rat TSCs.

Methods: Rat TSCs were isolated and cultured. ADAM8 overexpression plasmids were constructed to transfect rat TSCs. Cell viability, Apoptosis, osteogenic differentiation, and RUNX2/OCN mRNA expression were assessed using the CCK-8 assay, flow cytometry, Alizarin Red staining, and quantitative Real-Time PCR, respectively. Protein expression of RUNX2, OCN, as well as the phosphorylation levels of PI3K and Akt were detected using Western blot.

Results: ADAM8 overexpression led to inhibited TSC viability and increased Apoptosis. Simultaneously, ADAM8 overexpression also inhibited the osteogenic differentiation capacity of TSCs, evidenced by reduced ALP activity, fewer mineralized nodules, and decreased the expression of the osteogenesis-related genes RUNX2 and OCN. Further mechanistic studies demonstrated that ADAM8 overexpression significantly inhibited the phosphorylation levels of PI3K and Akt after osteogenic induction, but these changes were reversed by adding the PI3K agonist 740Y-P. Additionally, 740Y-P was also able to rescue the inhibitory effects of ADAM8 overexpression on TSC proliferation and osteogenic differentiation.

Conclusion: ADAM8 regulates the proliferation and osteogenic differentiation of rat TSCs through the PI3K/Akt signaling.

Keywords

ADAM8; PI3K/AKT; Tendon stem cell; Tendon-bone healing.

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