The inhibition of subchondral bone lesions significantly reversed the weight-bearing deficit and the overexpression of CGRP in DRG neurons, GFAP and Iba-1 in the spinal dorsal horn in the monosodium iodoacetate induced model of osteoarthritis pain.

Degang Yu,Yang Li,Xin Zhao,Zhenan Zhu,Xiaoqing Wang,Yuanqing Mao,Ming Liu,Fengxiang Liu,Theodore John Price

doi:10.1371/journal.pone.0077824

Abstract

BackgroundChronic pain is the most prominent and disabling symptom of osteoarthritis (OA). Clinical data suggest that subchondral bone lesions contribute to the occurrence of joint pain. The present study investigated the effect of the inhibition of subchondral bone lesions on joint pain.MethodsOsteoarthritic pain was induced by an injection of monosodium iodoacetate (MIA) into the rat knee joint. Zoledronic acid (ZOL), a third generation of bisphosphonate, was used to inhibit subchondral bone lesions. Joint histomorphology was evaluated using X-ray micro computed tomography scanning and hematoxylin-eosin staining. The activity of osteoclast in subchondral bone was evaluated using tartrate-resistant acid phosphatase staining. Joint pain was evaluated using weight-bearing asymmetry, the expression of calcitonin gene-related peptide (CGRP) in the dorsal root ganglion (DRG), and spinal glial activation status using glial fibrillary acidic protein (GFAP) and ionized calcium binding adaptor molecule-1 (Iba-1) immunofluorescence. Afferent neurons in the DRGs that innervated the joints were identified using retrograde fluorogold labeling.ResultsMIA injections induced significant histomorphological alterations and joint pain. The inhibition of subchondral bone lesions by ZOL significantly reduced the MIA-induced weight-bearing deficit and overexpression of CGRP in DRG neurons, GFAP and Iba-1 in the spinal dorsal horn at 3 and 6 weeks after MIA injection; however, joint swelling and synovial reaction were unaffected.ConclusionsThe inhibition of subchondral bone lesions alleviated joint pain. Subchondral bone lesions should be a key target in the management of osteoarthritic joint pain.

Highlights

Osteoarthritis (OA) is a leading cause of disability in elderly people, and it is characterized by a progressive loss of articular cartilage, subchondral bone lesions and synovitis [1]
The present study investigated the inhibition of subchondral bone lesions on osteoarthritic joint pain
The present study demonstrated that an injection 3 mg monosodium iodoacetate (MIA) induced obvious joint pathology and joint pain, which is consistent with previous results

Summary

Introduction

Osteoarthritis (OA) is a leading cause of disability in elderly people, and it is characterized by a progressive loss of articular cartilage, subchondral bone lesions and synovitis [1]. Accumulating clinical evidence suggests that abnormal subchondral bones are a primary source of joint pain in OA. Bone marrow lesions (BMLs) in the subchondral trabecular bone, which are ill-defined areas of high signal intensity on T2-weighted, fat-suppressed MRIs, are positively associated with knee pain in OA [10,11]. Immediate joint pain relief is usually accomplished by total or unicompartmental knee arthroplasty, in which the majority of the affected subchondral plate is excised [13]. These clinical findings suggest that subchondral bone lesions contribute to the occurrence of joint pain in OA. Clinical data suggest that subchondral bone lesions contribute to the occurrence of joint pain. The present study investigated the effect of the inhibition of subchondral bone lesions on joint pain

Methods

Results

Discussion

Conclusion