The study of chondrogenic progenitor cells (CPCs) as seed cells has become a new focus of cartilage regeneration. The inflammatory environment of osteoarthritis (OA) inhibits the repair ability of CPCs. But the OA patients’ CPCs showed an excellent regeneration ability with intermittent hydrostatic pressure (IHP). However, the mechanism is unclear. We compared the expression of the Hippo signaling effect factor YAP between OA and normal cartilages. Then, the relationship between the Kellgren-Lawrence (K-L) score of OA and the rate of YAP-positive cells was analyzed. The changes of CPCs after IHP and IL-1β applications were observed. The OA model was established by cutting the anterior cruciate ligament of rats. The knee joint of the OA rats was distracted by hinged external fixator to create suitable IHP, named as the IHP group. The IHP group plus intra-articular injection of Verteporfin (VP) was named as the IHP+VP group, and the untreated rat group was named as the CON group. Four and 8 weeks after the operation, the reparative effect was evaluated by MASSON staining and immunohistochemical staining. Lower levels of YAP1 and higher expressions of p-YAP1 were found in the OA group as compared to the normal group. IHP inhibited the Hippo signaling in an inflammatory environment and promoted the proliferation of CPCs. The cartilage deterioration in the CON group progressed more significantly than that in the IHP+VP group. The best reparative effect was observed in the IHP group with increased expression of YAP1 and decreased p-YAP1. These results hint that mechanical stress can activate CPCs and promote cartilage repair in an inflammatory environment through inhibiting Hippo signaling.
Background Adjacent segment disease (ASD) is a common complication after posterior lumbar interbody fusion (PLIF). Recently, a topping-off surgery (non-fusion with Coflex) has been developed to reduce the risk of ASD, yet whether and how the topping-off surgery can relieve ASD remains unclear. The purpose of this study was to explore the biomechanical effect of PLIF and Coflex on the adjacent segments via finite element (FE) analysis and discuss the efficacy of Coflex in preventing ASD.Methods A FE model of L3-5 segments was generated from the CT of a healthy volunteer via three commercially available software. Coflex and PLIF devices were modeled and implanted with the segment model in the FE software. In the FE model, a pre-compressive load of 500 N, which was equal to two thirds of the human body mass, was applied to the top surface of the L3. In addition, four types of moments (anteflexion, rear protraction, bending and axial rotation) set as 10 Nm were successively applied to the FE model combined with this pre-compressive load. Then the range of motion (ROM), the torsional rigidity and the maximum von Mises equivalent stress on L3-L4 disc and the implant were analyzed.Results Both Coflex and PLIF reduced ROM. However, no significant difference was found in the maximum von Mises equivalent stress of adjacent segment disc between the two devices. Interestingly enough, both systems increased the torsional rigidity at the adjacent lumbar segment, and PLIF had a more significant increase. The Coflex implant had a larger maximum von Mises equivalent stress.Conclusions Both Coflex and PLIF reduced ROM at L3-L4, and thus improved the lumbar stability. Under the same load, both devices had almost the same maximum von Mises equivalent stress as the normal model on the adjacent intervertebral disc. But it is worthy to notice the torsional rigidity of PLIF was higher than that of Coflex. It indicated that the lumbar treated with PLIF would undertake a larger load to reach ROM of Coflex. Therefore, we presumed that ADS was related to higher torsional rigidity.
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