Intra-Articular Injection of Umbilical Cord Mesenchymal Stem Cells Loaded With Graphene Oxide Granular Lubrication Ameliorates Inflammatory Responses and Osteoporosis of the Subchondral Bone in Rabbits of Modified Papain-Induced Osteoarthritis.

Aifeng Liu,Qinxin Zhou,Chao Zhang,Ye Yuan,Juntao Zhang,Puyu Niu,Jixin Chen

doi:10.3389/fendo.2021.822294

Abstract

AimThis study is to investigate the effects of umbilical cord mesenchymal stem cells (UCMSCs) loaded with the graphene oxide (GO) granular lubrication on ameliorating inflammatory responses and osteoporosis of the subchondral bone in knee osteoarthritis (KOA) animal models.MethodsThe KOA animal models were established using modified papain joint injection. 24 male New Zealand rabbits were classified into the blank control group, GO group, UCMSCs group, and GO + UCMSCs group, respectively. The concentration in serum and articular fluid nitric oxide (NO), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), type II collagen (COL-II), and glycosaminoglycan (GAG) was detected using ELISA, followed by the dissection of femoral condyles and staining of HE and Micro-CT for observation via the microscope.ResultsGO granular lubrication and UCMSCs repaired the KOA animal models. NO, IL-6, TNF-α, GAG, and COL-II showed optimal improvement performance in the GO + UCMSCs group, with statistical significance in contrast to the blank group (P <0.01). Whereas, there was a great difference in levels of inflammatory factors in serum and joint fluid. Micro-CT scan results revealed the greatest efficacy of the GO + UCMSCs group in improving joint surface damage and subchondral bone osteoporosis. HE staining pathology for femoral condyles revealed that the cartilage repair effect in GO + UCMSCs, UCMSCs, GO, and blank groups were graded down.ConclusionUCMSCs loaded with graphene oxide granular lubrication can promote the secretion of chondrocytes, reduce the level of joint inflammation, ameliorate osteoporosis of the subchondral bone, and facilitate cartilage repair.

Highlights

Knee osteoarthritis (KOA) is a degenerative bone and joint disease and most prevalent in the middle-aged and elderly [1]
The GO + UCMSCs group had a lower mean value of serum NO compared with the blank group
P values for serum and articular fluid in the GO + UCMSC group compared to the UCMSC group were 0.012 and 0.032 respectively

Summary

Introduction

Knee osteoarthritis (KOA) is a degenerative bone and joint disease and most prevalent in the middle-aged and elderly [1]. With the effect of aging and increasing obesity, KOA is expected to be the single biggest reason for disability by 2030. Apart from that, it has become a major public health issue along with the increasing morbidity of KOA [8,9,10]. Major non-pharmacological treatments such as physical therapy, medical education and self-management, weight loss, non-steroidal anti-inflammatory drugs, and intra-articular injections are recommended in the guidelines. These treatments only relieve pain and fail to slow down cartilage degeneration and promote cartilage repair [11]

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