Duration of postoperative immobilization affects MMP activity at the healing graft-bone interface: Evaluation in a mouse ACL reconstruction model.

Yusuke Nakagawa,Susumu Wada,Amir H Lebaschi,Dean Wang,Scott A Rodeo,Camilla B Carballo,Zoe M Album,Xiang‐Hua Deng,Samuel J E Green

doi:10.1002/jor.24177

Yusuke Nakagawa, Susumu Wada + Show 7 more

Open Access

https://doi.org/10.1002/jor.24177

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Abstract

Excessive MMP activity may impair tendon-to-bone healing. However, little is known about the effect of joint motion on MMP activity after ACL reconstruction. The aim of this study was to determine the effect of different durations of knee immobilization on MMP activity in a mouse ACL reconstruction model using a fluorescent MMP probe which detects MMP 2, 3, 9, and 13 and near-infra red in vivo imaging. Sixty C57BL male mice underwent ACL reconstruction. Post-operatively, the animals were treated with free cage activity (Group 1), or with the use of an external fixator to restrict knee motion and weight bearing for 5 days (Group 2), 14 days (Group 3), and 28 days (Group 4). At days 3, 7, 16, 23, and 30, five mice underwent IVIS imaging. At days 3, 7, 16, and 30, histological analysis was also performed. Probe signal intensity in the whole limb peaked at day 7, followed by a decrease at day 16, and maintenance up to day 30. There was no significant difference among groups at any time point based on IVIS, but histologic localization of MMP probe signal showed significantly less activity in Group 2 and Group 3 compared to Group 4 in the bone tunnel at day 30. We demonstrated that short-term immobilization led to less MMP activity around the bone tunnel compared with prolonged immobilization. A short period of immobilization after ACL reconstruction might enhance graft-bone interface healing by mitigating excess MMP expression. These findings have implications for post-operative rehabilitation protocols following ACL reconstruction. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:325-334, 2019.

Highlights

Successful ACL reconstruction using a tendon graft requires sufficient healing between the tendon and bone.[1,2] Delayed or incomplete graft healing after ACL reconstruction may be associated with poor clinical outcomes, including recurrent knee instability, reduced performance, and lower rates of return to sport
In prior work in our laboratory, we demonstrated that a period of immobilization following ACL reconstruction had positive effects on inflammation and bone formation along the healing tendon-bone interface compared with immediate motion after surgery.[12]
We aimed to investigate how different knee immobilization periods affected Matrix metalloproteinases (MMPs) activity at the healing graft-bone interface

Summary

Introduction

Successful ACL reconstruction using a tendon graft requires sufficient healing between the tendon and bone.[1,2] Delayed or incomplete graft healing after ACL reconstruction may be associated with poor clinical outcomes, including recurrent knee instability, reduced performance, and lower rates of return to sport. In the current study we used MMP680 Sense probe which is specific for MMP-2, −3, −9, and −13 and gives off near-infra red fluorescence These techniqueshave been extensively validated and used in studies of cancer[15] and atherosclerosis,[16] and have proven to be useful for studies of the musculoskeletal system such as bone metabolism[17] and OA.[18,19] as far as we know, there have been no reports utilizing this methodology to investigate tendon-to-bone healing. The aim of this study was to determine the effect of different knee immobilization periods on MMP activity in a mouse ACL reconstruction model using a fluorescent MMP probe and near-infra red in vivo imaging

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