scholarly journals Effect of Suppression of Rotational Joint Instability on Cartilage and Meniscus Degeneration in Mouse Osteoarthritis Model

2021 ◽  
Author(s):  
Kohei Arakawa ◽  
Kei Takahata ◽  
Yuichiro Oka ◽  
Kaichi Ozone ◽  
Kazuma Morosawa ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Joint Instability ◽  
Cartilage Degeneration ◽  
The Other ◽  
Rotational Instability ◽  
Tibial Rotation ◽  
Intact Group ◽  
Tnf Α ◽  
Meniscus Degeneration ◽  
Articular Cartilage Degeneration

Objective: Joint instability and meniscal dysfunction contribute to the onset and progression of knee osteoarthritis (OA). In the destabilization of the medial meniscus (DMM) model, secondary OA occurs due to the rotational instability and increases compressive stress resulting from the meniscal dysfunction. We created a new controlled abnormal tibial rotation (CATR) model that reduces the rotational instability that occurs in the DMM model. So, we aimed to investigate whether rotational instability affects articular cartilage degeneration using the DMM and CATR models, as confirmed using histology and immunohistochemistry. Design: Twelve-week-old male mice were randomized into 3 groups: DMM group, CATR group, and INTACT group (right knee of the DMM group). After 8 and 12 weeks, we performed the tibial rotational test, safranin-O/fast green staining, and immunohistochemical staining for TNF-α and MMP-13. Results: The rotational instability in the DMM group was significantly higher than that of the other groups. And articular cartilage degeneration was higher in the DMM group than in the other groups. However, meniscal degeneration was observed in both DMM and CATR groups. The TNF-α and MMP-13 positive cell rates in the articular cartilage of the CATR group were lower than those in the DMM group. Conclusions: We found that the articular cartilage degeneration was effectively suppressed by controlling the rotational instability caused by meniscal dysfunction. These findings suggest that suppression of rotational instability in the knee joint is an effective therapeutic measure for preventing OA progression.

scholarly journals Effect of differences in mechanical stress in vivo on the onset and progression of knee osteoarthritis

2021 ◽  
Author(s):  
Kohei Arakawa ◽  
Kei Takahata ◽  
Yuichiro Oka ◽  
Kaichi Ozone ◽  
Sumika Nakagaki ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Bone Formation ◽  
Mechanical Stress ◽  
Compressive Stress ◽  
Subchondral Bone ◽  
Shear Force ◽  
Joint Instability ◽  
Cartilage Degeneration ◽  
Articular Cartilage Degeneration

Objective: The effect of the type of mechanical stress on OA onset has not been clarified. The aim of this study was to establish a new model that reproduces the type and increase and decrease of mechanical stress in vivo and to clarify the differences in the mechanism of knee OA onset and progression among the models. Design: To reproduce the difference in mechanical stress, we used the anterior cruciate ligament transection (ACL-T) model and the destabilization of the medial meniscus (DMM) model. In addition, we created a controlled abnormal tibial translation (CATT) model and a controlled abnormal tibial rotation (CATR) model that suppressed the joint instability of the ACL-T and DMM model, respectively. These four models reproduced the increase and decrease in shear force due to joint instability and compressive stress due to meniscal dysfunction. We performed joint instability analysis with soft X-ray, micro computed tomography analysis, histological analysis, and immunohistological analysis in 4 and 6 weeks. Results: Joint instability decreased in the CATT and CATR groups. The meniscus deviated in the DMM and CATR groups. Chondrocyte hypertrophy increased in the ACL-T and DMM groups with joint instability. In the subchondral bone, bone resorption was promoted in the ACL-T and CATT groups, and bone formation was promoted in the DMM and CATR groups. Conclusions: Increased shear force causes articular cartilage degeneration and osteoclast activation in the subchondral bone. In contrast, increased compressive stress promotes bone formation in the subchondral bone earlier than articular cartilage degeneration occurs.

scholarly journals Joint Hemorrhage Accelerates Cartilage Degeneration in a Rat Immobilized Knee Model

2020 ◽  
Author(s):  
Yasuhito Sogi ◽  
Yutaka Yabe ◽  
Yoshihiro Hagiwara ◽  
Masahiro Tsuchiya ◽  
Yoshito Onoda ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Cartilage Degeneration ◽  
Male Rats ◽  
Mankin Score ◽  
Gene Expressions ◽  
Knee Model ◽  
Articular Fractures ◽  
Tnf Α ◽  
Significant Difference ◽  
Articular Cartilage Degeneration

Abstract Background: Joint hemorrhage is caused by trauma, ligament reconstruction surgery, and bleeding disorder such as hemophilia. Recurrence of hemorrhage in the joint space induces hemosiderotic synovitis as well as oxidative stress, resulting in both articular cartilage degeneration and arthropathy. Joint immobilization is a common treatment option for articular fractures accompanied by joint hemorrhage. Although it is apparent that joint hemorrhage is harmful on the articular cartilage, there was no consensus whether reduction of joint hemorrhage is effective to prevent articular cartilage degeneration. The purpose of this study was to investigate the articular cartilage degeneration induced by a combination of joint hemorrhage and joint immobilization in a rat knee model.Methods: The knee joints of adult male rats were immobilized at the flexion using an internal fixator from 3 days to 8 weeks. The rats were divided randomly into two groups: immobilized blood injection (Im-B) group and immobilized-normal saline injection (Im-NS) group. The cartilage was evaluated at two areas (contact and non-contact areas). The cartilage was assessed for the chondrocyte count, Modified Mankin score, and cartilage thickness. Total RNA was extracted from the cartilage in both areas, and gene expressions of metalloproteinase (MMP)-8, MMP-13, interleukin (IL)-1β, and tumor necrosis factor (TNF)-α were measured by quantitative real-time polymerase chain reaction.Results: The number of chondrocytes in the Im-B group significantly decreased in both areas, compared to the Im-NS group. Modified Mankin score from 4–8 weeks of the Im-B group was significantly greater than the Im-NS group only in the contact area. Gene expressions of MMP-8 and MMP-13 from 2–4 weeks and TNF-α from 2–8 weeks significantly increased in the Im-B group compared to the Im-NS group, while there was no significant difference in IL-1β.Conclusions: This study showed that joint hemorrhage exacerbated immobilization-induced articular cartilage degeneration. Therefore, drainage of a joint hemorrhage and avoidance of loading are recommended to prevent cartilage degeneration during immobilization of a joint hemorrhage.

scholarly journals Joint hemorrhage accelerates cartilage degeneration in a rat immobilized knee model

2020 ◽  
Author(s):  
Yasuhito Sogi ◽  
Yutaka Yabe ◽  
Yoshihiro Hagiwara ◽  
Masahiro Tsuchiya ◽  
Yoshito Onoda ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Cartilage Degeneration ◽  
Joint Space ◽  
Male Rats ◽  
Mankin Score ◽  
Knee Model ◽  
Articular Fractures ◽  
Tnf Α ◽  
Significant Difference ◽  
Articular Cartilage Degeneration

Abstract Background: Joint hemorrhage is caused by trauma, ligament reconstruction surgery, and bleeding disorders such as hemophilia. Recurrence of hemorrhage in the joint space induces hemosiderotic synovitis and oxidative stress, resulting in both articular cartilage degeneration and arthropathy. Joint immobilization is a common treatment option for articular fractures accompanied by joint hemorrhage. Although it is apparent that joint hemorrhage has negative effects on the articular cartilage, there is no consensus whether a reduction in joint hemorrhage is effective to prevent articular cartilage degeneration. The purpose of this study was to investigate the articular cartilage degeneration induced by a combination of joint hemorrhage and joint immobilization in a rat immobilized knee model. Methods: The knee joints of adult male rats were immobilized at the flexion using an internal fixator from 3 days to 8 weeks. The rats were randomly divided into the following groups: immobilized blood injection (Im-B) and immobilized-normal saline injection (Im-NS) groups. The cartilage was evaluated in two areas (contact and non-contact areas). The cartilage was used to assess chondrocyte count, Modified Mankin score, and cartilage thickness. The total RNA was extracted from the cartilage in both areas, and the expression of metalloproteinase (MMP)-8, MMP-13, interleukin (IL)-1β, and tumor necrosis factor (TNF)-α was measured by quantitative real-time polymerase chain reaction. Results: The number of chondrocytes in the Im-B group significantly decreased in both areas, compared with that in the Im-NS group. Modified Mankin score from 4–8 weeks of the Im-B group was significantly higher than that of the Im-NS group only in the contact area. The expression of MMP-8 and MMP-13 from 2 to 4 weeks and TNF-α from 2 to 8 weeks significantly increased in the Im-B group compared with those in the Im-NS group, but there was no significant difference in IL-1β expression. Conclusions: The results showed that joint hemorrhage exacerbated immobilization-induced articular cartilage degeneration. Drainage of a joint hemorrhage or avoidance of loading may help prevent cartilage degeneration during joint immobilization with a hemorrhage.

The Effect of Total Meniscectomy versus Caudal Pole Hemimeniscectomy on the Stifle Joint of the Sheep

1999 ◽  
Vol 12 (02) ◽  
pp. 56-63 ◽  
Author(s):  
C. R. Bellenger ◽  
P. Ghosh ◽  
Y. Numata ◽  
C. Little ◽  
D. S. Simpson
Keyword(s):  
Tissue Culture ◽  
Articular Cartilage ◽  
Fibrous Tissue ◽  
Cartilage Degeneration ◽  
Medial Compartment ◽  
Proteoglycan Synthesis ◽  
Stifle Joint ◽  
Medial Meniscectomy ◽  
Tibial Condyle ◽  
Articular Cartilage Degeneration

SummaryTotal medial meniscectomy and caudal pole hemimeniscectomy were performed on the stifle joints of twelve sheep. The two forms of meniscectomy produced a comparable degree of postoperative lameness that resolved within two weeks of the operations. After six months the sheep were euthanatised and the stifle joints examined. Fibrous tissue that replaced the excised meniscus in the total meniscectomy group did not cover as much of the medial tibial condyle as the residual cranial pole and caudal fibrous tissue observed following hemimeniscectomy. The articular cartilage from different regions within the joints was examined for gross and histological evidence of degeneration. Analyses of the articular cartilage for water content, glycosaminoglycan composition and DNA content were performed. The proteoglycan synthesis and release from explanted articular cartilage samples in tissue culture were also measured. There were significant pathological changes in the medial compartment of all meniscectomised joints. The degree of articular cartilage degeneration that was observed following total meniscectomy and caudal pole meniscectomy was similar. Caudal pole hemimeniscectomy, involving transection of the meniscus, causes the same degree of degeneration of the stifle joint that occurs following total meniscectomy.The effect of total medial meniscectomy versus caudal pole hemimeniscectomy on the stifle joint of sheep was studied experimentally. Six months after the operations gross pathology, histopathology, cartilage biochemical analysis and the rate of proteoglycan synthesis in tissue culture were used to compare the articular cartilage harvested from the meniscectomised joints. Degeneration of the articular cartilage from the medial compartment of the joints was present in both of the groups. Caudal pole hemimeniscectomy induces a comparable degree of articular cartilage degeneration to total medial meniscectomy in the sheep stifle joint.

MOLECULAR CONTROL OF ARTICULAR CARTILAGE DEGENERATION BY TRANSFORMING GROWTH FACTOR ALPHA

2008 ◽  
Vol 31 (4) ◽  
pp. 2
Author(s):  
Tom Appleton ◽  
Shirine Usmani ◽  
John Mort ◽  
Frank Beier
Keyword(s):  
Gene Expression ◽  
Articular Cartilage ◽  
Growth Factor ◽  
P38 Mapk ◽  
Transforming Growth Factor ◽  
Cartilage Degeneration ◽  
Signalling Pathways ◽  
Transforming Growth Factor Alpha ◽  
Factor Alpha ◽  
Articular Cartilage Degeneration

Background: Articular cartilage degeneration is a hallmark of osteoarthritis (OA). We previously identified increased expression of transforming growth factor alpha (TGF?) and chemokine (C-C motif) ligand 2 (CCL2) in articular cartilage from a rat modelof OA (1,2). We subsequently reported that TGF? signalling modified chondrocyte cytoskeletal organization, increased catabolic and decreased anabolic gene expression and suppressed Sox9. Due to other roles in chondrocytes, we hypothesized that the effects ofTGF? on chondrocytes are mediated by Rho/ROCK and MEK/ERK signaling pathways. Methods: Primary cultures of chondrocytes and articularosteochondral explants were treated with pharmacological inhibitors of MEK1/2(U0126), ROCK (Y27632), Rho (C3), p38 MAPK (SB202190) and PI3K (LY294002) to elucidate pathway involvement. Results: Using G-LISA we determined that stimulation of primary chondrocytes with TGF? activates RhoA. Reciprocally, inhibition of RhoA/ROCK but not other signalling pathways prevents modification of the actin cytoskeleton in responseto TGF?. Inhibition of MEK/ERKsignaling rescued suppression of anabolic gene expression by TGF? including SOX9 mRNA and protein levels. Inhibition of MEK/ERK, Rho/ROCK, p38 MAPK and PI3K signalling pathways differentially controlled the induction of MMP13 and TNF? gene expression. TGF? also induced expression of CCL2 specifically through MEK/ERK activation. In turn, CCL2 treatment induced the expression of MMP3 and TNF?. Finally, we assessed cartilage degradation by immunohistochemical detection of type II collagen cleavage fragments generated by MMPs. Blockade of RhoA/ROCK and MEK/ERK signalling pathways reduced the generation of type IIcollagen cleavage fragments in response to TGF? stimulation. Conclusions: Rho/ROCK signalling mediates TGF?-induced changes inchondrocyte morphology, while MEK/ERK signalling mediates the suppression ofSox9 and its target genes, and CCL2 expression. CCL2, in turn, induces the expression of MMP3 and TNF?, two potent catabolic factors known to be involved in OA. These pathways may represent strategic targets for interventional approaches to treating cartilage degeneration in osteoarthritis. References: 1. Appleton CTG et al. Arthritis Rheum 2007;56:1854-68. 2. Appleton CTG et al. Arthritis Rheum 2007; 56:3693-705.

scholarly journals Early patellofemoral articular cartilage degeneration in a rat model of patellar instability is associated with activation of the NF-κB signaling pathway

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Wei Lin ◽  
Huijun Kang ◽  
Yike Dai ◽  
Yingzhen Niu ◽  
Guangmin Yang ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Signaling Pathway ◽  
Subchondral Bone ◽  
Patellofemoral Joint ◽  
Patellar Instability ◽  
Cartilage Degeneration ◽  
Control Group ◽  
And Control ◽  
Articular Cartilage Degeneration ◽  
And Cartilage

Abstract Background Patellar instability (PI) often increases the possibility of lateral patellar dislocation and early osteoarthritis. The molecular mechanism of early articular cartilage degeneration during patellofemoral osteoarthritis (PFOA) still requires further investigation. However, it is known that the NF-κB signaling pathway plays an important role in articular cartilage degeneration. The aim of this study was to investigate the relationship between the NF-κB signaling pathway and patellofemoral joint cartilage degeneration. Methods We established a rat model of PI-induced PFOA. Female 4-week-old Sprague-Dawley rats (n = 120) were randomly divided into two groups: the PI (n = 60) and control group (n = 60). The distal femurs of the PI and control group were isolated and compared 4, 8, and 12 weeks after surgery. The morphological structure of the trochlear cartilage and subchondral bone were evaluated by micro-computed tomography and histology. The expression of NF-κB, matrix metalloproteinase (MMP)-13, collagen X, and TNF-ɑ were evaluated by immunohistochemistry and quantitative polymerase chain reaction. Results In the PI group, subchondral bone loss and cartilage degeneration were found 4 weeks after surgery. Compared with the control group, the protein and mRNA expression of NF-κB and TNF-ɑ were significantly increased 4, 8, and 12 weeks after surgery in the PI group. In addition, the markers of cartilage degeneration MMP-13 and collagen X were more highly expressed in the PI group compared with the control group at different time points after surgery. Conclusions This study has demonstrated that early patellofemoral joint cartilage degeneration can be caused by PI in growing rats, accompanied by significant subchondral bone loss and cartilage degeneration. In addition, the degeneration of articular cartilage may be associated with the activation of the NF-κB signaling pathway and can deteriorate with time as a result of PI.

Effect of Remnant-Preserving Reconstruction of Acute Anterior Cruciate Ligament Injuries in a Rabbit Model: Histological and Biomechanical Analysis

2022 ◽  
Vol 12 (5) ◽  
pp. 897-906
Author(s):  
XiaoChen Ju ◽  
Hao Chai ◽  
Sasirekha Krishnan ◽  
Abinaya Jaisankar ◽  
Murugan Ramalingam ◽  
...  
Keyword(s):  
Anterior Cruciate Ligament ◽  
Articular Cartilage ◽  
Acl Reconstruction ◽  
Bone Healing ◽  
Cruciate Ligament ◽  
Cartilage Degeneration ◽  
Remnant Preservation ◽  
Model Animal ◽  
Anterior Cruciate ◽  
Articular Cartilage Degeneration

Acute anterior cruciate ligament (ACL) is a key structure that stabilizes knee joints. The objective of this research is to investigate the influence of ligament remnants preserved on the tendon-bone healing following ACL reconstruction and to examine postoperative articular cartilage degeneration in rabbit as a model animal. Sixty New Zealand rabbits are randomly divided into an ACL reconstruction without remnant preservation group (Group A; n = 30) or ACL reconstruction with remnant preservation group (Group B; n = 30). The expression of HIF-1α, VEGF, and micro vessel density (MVD) in the transplanted tendon was detected by immunohistochemical staining at week 6 and 12 after the operation. The signal intensity of the transplanted tendon was observed by MRI scanning, and the width of the bone tunnel was measured by CT scanning at week 6 and 12 after the operation. The graft biomechanics was tested 12 weeks after the operation. The JNK and MMP-13 expression levels were compared to analyze the cartilage degeneration of the knee at week 12 after the operation. The experimental results were analyzed and showed that the remnant-preserving ACL reconstruction is beneficial for bone healing of the tendon in rabbits, but ACL reconstruction with or without ligament remnants preserved will not affect knee articular cartilage degeneration post-surgery.

Symptomatic Articular Cartilage Degeneration

2001 ◽  
Vol 391 ◽  
pp. S14-S25 ◽  
Author(s):  
Douglas W. Jackson ◽  
Timothy M. Simon ◽  
Harold M. Aberman
Keyword(s):  
Articular Cartilage ◽  
Cartilage Degeneration ◽  
Articular Cartilage Degeneration
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