Controlling joint instability delays the degeneration of articular cartilage in a rat model

Murata, Kenji; Kanemura, Naohiko; Kokubun, Takanori; Fujino, Tsutomu; Morishita, Yuri; Onitsuka, Katsuya; Fujiwara, Shuhei; Nakajima, Aya; Shimizu, Dai; Takayanagi, Kunio

doi:10.1016/j.joca.2016.10.011

Cited by 37 publications

(69 citation statements)

References 40 publications

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“…In order to verify the protective effect of EAF from SSG on OA development, in the present study, we evaluated the in vivo antiosteoarthritic effect of intra-articular administration of EAF from SSG on a classical rat OA model surgically induced by ACLT. This OA animal model is characterized by joint instability, intra-articular inflammation and structural joint changes, which are similar to typical osteoarthritic features observed in human OA [7,8]. Our findings would be helpful to uncover the modern pharmacological aspects of SSG, and lay the experimental foundation for the better clinical application or food therapy of SSG for OA control.…”

Section: Introductionsupporting

confidence: 56%

“…After a 1-week acclimation period, all animals were randomly divided into 3 groups of 12 rats in each group: (1) shamoperated control group; (2) ACLT OA model control group; (3) ACLT+ intra-articular administation of EAF from SSG group. The anterior cruciate ligaments in the right knees of rats in 2 and 3 groups were surgically transected as previously described [7][8][9] to establish OA model. Arthrotomy without anterior cruciate ligament damage was performed in sham-operated rats.…”

Section: Animals and Groupsmentioning

confidence: 99%

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Protective effect of ethyl acetate fraction from Semen sojae germinatum, the processed sprout of Chinese black soybean, on rat experimental osteoarthritis

Wang

Guo

et al. 2020

BMC Complement Med Ther

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Background: Our previous in vitro study reported that the ethyl acetate fraction (EAF) of Semen sojae germinatum (SSG), the processed sprout of Chinese black soybean, possessed the potent anti-inflammatory and chondroprotective properties. The aim of the present work was to verify the in vivo antiosteoarthritic effect of EAF from SSG on a rat osteoarthritis (OA) model. Methods: A classical rat OA model was surgically induced by anterior cruciate ligament transaction (ACLT). The OA rats were intra-articularly administered EAF from SSG for 8 weeks. The cartilage and synovial tissues were stained with hematoxylin and eosin (HE) to observe the histopathological changes. Safranin O/fast green staining was used to assess the glycosaminoglycan content in cartilage tissue sections. The expression of type II collagen and matrix metalloproteinase (MMP)-13 in cartilage was measured by immunohistochemistry. The apoptotic chondrocytes in the cartilage sections were detected using TUNEL assay. The concentrations of interleukin (IL)-1β and tumor necrosis factor (TNF)-ɑ in synovial fluid were determined using ELISA. Results: Intra-articular administration of EAF from SSG well retained the structure and superficial layer of cartilage tissues, ameliorated cartilage lesion and the degradation of cartilage matrix, including proteoglycan and type II collagen, induced by ACLT operation. The ACLT-induced upregulation of MMP-13 expression in the cartilage tissues was resisted by EAF from SSG. Moreover, EAF from SSG inhibited the ACLT-induced chondrocyte apoptosis. Compared to OA model group, the inflammatory status of synovial membrane was improved, the levels of inflammatory cytokines IL-1β and TNF-ɑ in synovial fluid were decreased in rats administrated with EAF from SSG. Conclusion: These data suggested that EAF from SSG displayed in vivo protective effect on OA development via preventing the degeneration of articular cartilage, inhibiting chondrocyte apoptosis and suppressing synovial inflammation.

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Section: Introductionsupporting

confidence: 56%

Section: Animals and Groupsmentioning

confidence: 99%

Protective effect of ethyl acetate fraction from Semen sojae germinatum, the processed sprout of Chinese black soybean, on rat experimental osteoarthritis

Wang

Guo

et al. 2020

BMC Complement Med Ther

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“…These previous studies pointed out that it is important to move articulation closer to normal and move it for protecting from early phase after injury. In addition, previous studies have shown that controlling abnormal joint movement in a completely ruptured ACL results in the down-regulation of inflammatory responses [ 33 ] and leads to spontaneous healing [ 27 ]. Furthermore, importance of weight-bearing has been pointed out in previous study [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

“…Prior research showed that changing the joint kinematics of a knee with complete ruptured ACL results in the down-regulation of inflammatory responses [ 33 ] and leads to spontaneous healing [ 27 ]. These previous studies used the CAM model used for the purpose of controlling abnormal knee joint movement without restricted knee flexion (Fig.…”

Section: Methodsmentioning

confidence: 99%

Effects of controlled abnormal joint movement on the molecular biological response in intra-articular tissues during the acute phase of anterior cruciate ligament injury in a rat model

Nishikawa

Kokubun

Kanemura

et al. 2018

BMC Musculoskelet Disord

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BackgroundThe anterior cruciate ligament (ACL) is responsible for braking forward movement of the tibia relative to the femur and for tibial rotation. After ACL injury, this braking performance deteriorates, inducing abnormal joint movement. The purpose of this study was to clarify the effects of controlled abnormal joint movement on the molecular biological response in intra-articular tissues during the acute phase of ACL injury.MethodsEighty-four mature Wistar male rats were randomly assigned to a controlled abnormal movement (CAM) group, an ACL-transection (ACL-T) group, a sham-operated group, or an intact group. The ACL was completely transected at its midportion in the ACL-T and CAM groups, and a nylon suture was used to control abnormal tibial translation in the CAM group. The sham-operated group underwent skin and joint capsule incisions and tibial drilling without ACL transection. Animals were not restricted activity until sacrifice 1, 3, or 5 days after surgery for histological and gene expression assessments. Acute-phase inflammation requires an important balance between degenerative and biosynthetic processes and is controlled by the activities of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). Both types of gene were analyzed in this study.ResultsThe ACL-T and CAM groups exhibited cleavage of the ACL at all time points. However, for the CAM group, the gap in the ligament stump was extremely small, and fibroblast proliferation was observed around the stump. Relative to the ACL-T group, the CAM group demonstrated significantly lower expression of MMP-13 mRNA and a lower MMP-13/TIMP-1 ratio on days 1 and 5 in the ACL, the medial meniscus and the lateral meniscus. The expression of TIMP-1 mRNA was not significantly different between the ACL-T and CAM groups.ConclusionsThe study results suggested that controlling abnormal movement inhibited the inflammatory reaction in intra-articular tissues after ACL injury. This reaction was down-regulated in intra-articular tissues in the CAM group. Abnormal joint control caused prolonged inflammation and inhibited remodeling during the acute phase of ACL rupture.

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“…This procedure was adapted from Murata et al . Both hindlimbs were harvested at 4 weeks postsurgery.…”

Section: Methodsmentioning

confidence: 99%

Cells from a GDF5 origin produce zonal tendon‐to‐bone attachments following anterior cruciate ligament reconstruction

Hagiwara

Dyrna

Kuntz

et al. 2019

Annals of the New York Academy of Sciences

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Following anterior cruciate ligament (ACL) reconstruction surgery, a staged repair response occurs where cells from outside the tendon graft participate in tunnel integration. The mechanisms that regulate this process, including the specific cellular origin, are poorly understood. Embryonic cells expressing growth and differentiation factor 5 (GDF5) give rise to several mesenchymal tissues in the joint and epiphyses. We hypothesized that cells from a GDF5 origin, even in the adult tissue, would give rise to cells that contribute to the stages of repair. ACLs were reconstructed in Gdf5-Cre;R26R-tdTomato lineage tracing mice to monitor the contribution of Gdf5-Cre;tdTom + cells to the tunnel integration process. Anterior−posterior drawer tests demonstrated 58% restoration in anterior−posterior stability. Gdf5-Cre;tdTom + cells within the epiphyseal bone marrow adjacent to tunnels expanded in response to the injury by 135-fold compared with intact controls to initiate tendon-to-bone attachments. They continued to mature the attachments yielding zonal insertion sites at 4 weeks with collagen fibers spanning across unmineralized and mineralized fibrocartilage and anchored to the adjacent bone. The zonal attachments possessed tidemarks with concentrated alkaline phosphatase activity similar to native entheses. This study established that mesenchymal cells from a GDF5 origin can contribute to zonal tendon-to-bone attachments within bone tunnels following ACL reconstruction.

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Controlling joint instability delays the degeneration of articular cartilage in a rat model

Abstract: Re-stabilization of joint instability may suppress inflammatory cytokines, thereby delaying the progression of OA. Joint instability is a substantial contributor to cartilage degeneration.

Cited by 37 publications

References 40 publications

Protective effect of ethyl acetate fraction from Semen sojae germinatum, the processed sprout of Chinese black soybean, on rat experimental osteoarthritis

Protective effect of ethyl acetate fraction from Semen sojae germinatum, the processed sprout of Chinese black soybean, on rat experimental osteoarthritis

Effects of controlled abnormal joint movement on the molecular biological response in intra-articular tissues during the acute phase of anterior cruciate ligament injury in a rat model

Cells from a GDF5 origin produce zonal tendon‐to‐bone attachments following anterior cruciate ligament reconstruction

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