Halofuginone attenuates articular cartilage degeneration by inhibition of elevated TGF‑β1 signaling in articular cartilage in a rodent osteoarthritis model

Mol Med Rep. 2017 Nov;16(5):7679-7684. doi: 10.3892/mmr.2017.7549. Epub 2017 Sep 20.

Abstract

Osteoarthritis (OA) is the most common degenerative condition of the weight‑bearing joints worldwide without effective medical therapy. In order to investigate whether administration of halofuginone (HF) may attenuate OA, the present study allocated 3‑month‑old male mice into Sham group, vehicle‑treated anterior cruciate ligament transection (ACLT) group and HF‑treated ACLT group. The present study determined that HF treatment reduced the expression of matrix metallopeptidase‑13 and collagen X in articular cartilage. Additionally, it lowered the Osteoarthritis Research Society International‑Modified Mankin score and prevented the loss of articular cartilage from Safranin O and Fast Green staining. HF reduced the progression of osteoarthritis by downregulating abnormally elevated TGF‑β1 activity in articular cartilage. Administration of HF may be a potential preventive therapy for OA.

MeSH terms

  • Animals
  • Anterior Cruciate Ligament / drug effects
  • Anterior Cruciate Ligament / metabolism
  • Anterior Cruciate Ligament / pathology
  • Anti-Inflammatory Agents / pharmacology*
  • Cartilage, Articular / drug effects*
  • Cartilage, Articular / metabolism
  • Cartilage, Articular / pathology
  • Collagen Type X / antagonists & inhibitors
  • Collagen Type X / genetics
  • Collagen Type X / metabolism
  • Disease Models, Animal
  • Gene Expression Regulation
  • Male
  • Matrix Metalloproteinase 13 / genetics
  • Matrix Metalloproteinase 13 / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Osteoarthritis / drug therapy*
  • Osteoarthritis / genetics
  • Osteoarthritis / metabolism
  • Osteoarthritis / pathology
  • Piperidines / pharmacology*
  • Quinazolinones / pharmacology*
  • Signal Transduction
  • Transforming Growth Factor beta1 / antagonists & inhibitors
  • Transforming Growth Factor beta1 / genetics*
  • Transforming Growth Factor beta1 / metabolism

Substances

  • Anti-Inflammatory Agents
  • Collagen Type X
  • Piperidines
  • Quinazolinones
  • Transforming Growth Factor beta1
  • Matrix Metalloproteinase 13
  • Mmp13 protein, mouse
  • halofuginone