Abstract
Osteoarthritis (OA) is a degenerative joint disease characterized by a progressive loss of articular cartilage. Mesenchymal stem cells transplanted to damaged tissues are promising for OA cartilage repair. However, these cells are poor survival after transplantation and acquire hypertrophic properties during chondrogenic induction. Parathyroid hormone-related protein (PTHrP) promotes chondrogenesis and suppresses chondrocyte hypertrophic differentiation. Additionally, PTHrP was reported to have anti-oxidant effects. The synthetic PTHrP(1-34) analog abaloparatide (ABL) is a newly approved drug for osteoporosis therapy. It is unknown whether ABL stimulates chondrogenesis and affects intracellular reactive oxygen species (ROS) production. By using mouse embryonic limb bud mesenchymal stem cells in micromass culture as an in vitro model of chondrogenic differentiation, we found that mesenchymal stem cells in micromass cultures spontaneously produced ROS, and N-acetyl-l-cysteine, a potent antioxidant, enhanced chondrogenesis. The effect of ABL on stimulation of chondrogenesis is involved in its inhibition of intracellular ROS generation. These novel findings support the use of ABL for the damaged cartilage regeneration.