Erythropoietin Enhances Meniscal Regeneration And Prevents Osteoarthritis Formation In Mice

BackgroundMeniscus injury plays a key role in the pathogenesis of osteoarthritis(OA).Long-term clinical observation confirmed that partial resection after meniscus tear could not reduce the incidence of OA.If meniscus injury cannot be treated in time,it can induce joint inflammation,cause biomechanical changes in joints,and lead to the formation of OA.Therefore,it is urgent to find drugs that can promote meniscus regeneration and delay or reverse the course of OA.Previous animal studies have reported that erythropoietin(EPO)promotes fracture healing and cartilage repair.ObjectiveThe purpose of this research is to study the development process of meniscus in mice,and to study the effects of cartilage repair-related growth factors and EPO on meniscus cells,focusing on joint formation,cartilage formation,angiogenesis,inflammation and matrix metabolism,we also established a mice A meniscus organ culture system,which was used to detect the effects of selected growth factors and revealed the effect of EPO on meniscus injury-induced OA(MIO)in mice.Methods1.First,to study the developmental pattern of mouse meniscus,the knee joint samples of mouse during the embryonic period and a certain period after birth are collected for histological and immunohistochemical studies.2.Cell culture studies were conducted by separating meniscus cells,and the results showed that EPO had the ability to promote cell proliferation,matrix protein production and neovascularization.3.An in vitro culture system for mouse meniscus organs was established.After in vitro culture and treatment,RNA and protein were extracted for RT-PCR and Western Blotting.Tissue sections can also be used for histological and immunohistochemical staining.4.By comparing the MIO and control groups at the 1st,5th and 9th postoperative week,the results show that early intervention is the most effective,and EPO can significantly reduce the severity of MIO,which may be related to enhanced meniscus regeneration.Results1.By studying the development of the meniscus in mice,some basic data on the proliferation,apoptosis and Col-1 distribution of meniscus cells were obtained,suggesting that the proliferation and apoptosis of meniscus cells before and after birth occur simultaneously2.Cell culture studies were conducted by separating meniscus cells,and the results showed that EPO had the ability to promote cell proliferation,matrix protein production,and neovascularization.3.In vitro culture of organs from the meniscus of the mouse showed that EPO up-regulated the expression of Col-1,Col-2 and VEGF-A,and down-regulated the expression of MMP-13.It shows that EPO has the ability to promote cell proliferation,matrix protein production and neovascularization,and inhibit joint inflammation.4.By comparing the intervention of EPO/PBS in different periods,samples of knee joints were collected for tissue staining.The results show that early intervention is the most effective,and EPO can significantly reduce the severity of MIO,which may be related to enhanced meniscus regenerationConclusion1.EPO can inhibit the expression of meniscus metalloproteinase MMP-13,and up-regulate the expression of Col-1,Col-2,and VEGF-A,thus inhibiting joint inflammation and promoting meniscus regeneration and repair.2.EPO may become an effective DMOAD,which can be used for the early treatment of meniscus injury and has the optimal effect on meniscus regeneration to prevent the progression of OA.