Baicalein Accelerates Tendon-Bone Healing via Activation of Wnt/ β-Catenin Signaling Pathway in Rats

Biomed Res Int. 2018 Mar 6:2018:3849760. doi: 10.1155/2018/3849760. eCollection 2018.

Abstract

Background: Tendon-bone healing is a reconstructive procedure which requires a tendon graft healing to a bone tunnel or to the surface of bone after the junction injury between tendon, ligament, and bone. The surgical reattachment of tendon to bone often fails due to regeneration failure of the specialized tendon-bone junction.

Materials and methods: An extra-articular tendon-bone healing rat model was established to discuss the effect of the baicalein 10 mg/(kg·d) in accelerating tendon-bone healing progress. Also, tendon-derived stem cells (TDSCs) were treated with various concentrations of baicalein or dickkopf-1 (DKK-1) to stimulate differentiation for 14 days.

Results: In vivo, tendon-bone healing strength of experiment group was obviously stronger than the control group in 3 weeks as well as in 6 weeks. And there were more mature fibroblasts, more Sharpey fibers, and larger new bone formation area treated intragastrically with baicalein compared with rats that were treated with vehicle for 3 weeks and 6 weeks. In vitro, after induction for 14 days, the expressions of osteoblast differentiation markers, that is, alkaline phosphatase (ALP), runt-related transcription factor 2 (Runx2), osteocalcin (OCN), osterix (OSX), and collagen I, were upregulated and Wnt/β-catenin signaling pathway was enhanced in TDSCs. The effect of DKK-1 significantly reduced the effect of baicalein on the osteogenic differentiation.

Conclusion: These data suggest that baicalein may stimulate TDSCs osteogenic differentiation via activation of Wnt/β-catenin signaling pathway to accelerate tendon-bone healing.

MeSH terms

  • Alkaline Phosphatase / metabolism
  • Animals
  • Bone and Bones / drug effects*
  • Bone and Bones / metabolism
  • Cell Differentiation / drug effects
  • Cells, Cultured
  • Core Binding Factor Alpha 1 Subunit / metabolism
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Flavanones / pharmacology*
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Male
  • Mesenchymal Stem Cells / drug effects
  • Mesenchymal Stem Cells / metabolism
  • Osteoblasts / drug effects
  • Osteoblasts / metabolism
  • Osteocalcin / drug effects
  • Osteocalcin / metabolism
  • Osteogenesis / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Stem Cells / drug effects
  • Stem Cells / metabolism
  • Tendons / drug effects*
  • Tendons / metabolism
  • Wnt Signaling Pathway / drug effects*
  • Wound Healing / drug effects*
  • beta Catenin / metabolism*

Substances

  • Core Binding Factor Alpha 1 Subunit
  • Flavanones
  • Intercellular Signaling Peptides and Proteins
  • beta Catenin
  • Osteocalcin
  • baicalein
  • Alkaline Phosphatase