Optimal Intra-articular Injection of Parathyroid Hormone-Related Protein Effectively Promotes Osteochondral Defects Repair

Terminal differentiation often occurs in the repair progress of osteochondral defects. It is reported that parathyroid hormone-related protein (PTHrP) could inhibit terminal differentiation but may elicit adverse effects on chondrogenesis when administrated at improper time. Here we apply PTHrP by optimal intra-articular injection together with implantation of a collagen-silk scaffold to treat osteochondral defect. The injection schedule was set at three different time windows: 4-6, 7-9 and 10-12 weeks post-operatively. Samples were obtained and evaluated macroscopically, histologically and immunohistochemically at 16 weeks post-injury. In vivo delivery of PTHrP at 4-6 weeks exhibited better repairing effects and less terminal differentiation compared with other time windows. These results showed that PTHrP would invoke best repair effects for osteochondral defects when intraarticularly injected at 4-6 weeks post-injury, which not only prevented terminal differentiation but also promoted cartilage regeneration in rabbit model. The findings offer insight into understanding the mechanisms involved and pave the way for clinical application of PTHrP for osteochondral defects repair.