scholarly journals The alteration of A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) in the knee joints of osteoarthritis mice

2019 ◽  
Author(s):  
Luling Wang ◽  
Demao Zhang ◽  
Jianxun Sun ◽  
Yujia Cui ◽  
Linyi Cai ◽  
...  

Abstract Background: To clarify the expression and distribution of ADAMTS1, ADAMTS2 and ADAMTS5 in knee joints of osteoarthritis (OA) mice. Methods: OA was established via anterior cruciate ligament transection (ACLT) on the knee joints of C57BL/6J mice. The morphology change of OA was analyzed by Micro-CT. Histologic analysis was used to evaluate symptomatic change in articular cartilage and subchondral bone. Quantitative real-time PCR (qPCR) was used to analyze mRNA expressions of ADAMTS family in bone-related tissues and cells. Immunofluorescence staining was used to analyze the expressions and distributions of ADAMTS1, ADAMTS2, and ADAMTS5, as well as the condition of inflammation of OA.Results: Cartilage deterioration, significant reduction of collagen and proteoglycan components in the cartilage matrix happened in ACLT-induced OA mice, along with increased inflammatory response and osteoclast activity. Among ADAMTS, the gene expression levels of ADAMTS1, ADAMTS2 and ADAMTS5 were ranked top 5 in cartilage/chondrocytes, osteogenic tissue/osteoblasts and cortical bone/osteocytes. After ACLT surgery, the expressions of ADAMTS1, ADAMTS2 and ADAMTS5 all increased in articular cartilage, growth plate and subchondral bone of knee joints. Conclusion: The enhanced expressions of ADAMTS1, ADAMTS2 and ADAMTS5 after ACLT surgery provide a further understanding in degenerative change of OA.

Cartilage ◽  
2019 ◽  
pp. 194760351987847 ◽  
Author(s):  
Nik Aizah ◽  
Pan Pan Chong ◽  
Tunku Kamarul

Objective Advances in research have shown that the subchondral bone plays an important role in the propagation of cartilage loss and progression of osteoarthritis (OA), but whether the subchondral bone changes precede or lead to articular cartilage loss remains debatable. In order to elucidate the subchondral bone and cartilage changes that occur in early OA, an experiment using anterior cruciate ligament transection (ACLT) induced posttraumatic OA model of the rat knee was conducted. Design Forty-two Sprague Dawley rats were divided into 2 groups: the ACLT group and the nonoperated control group. Surgery was conducted on the ACLT group, and subsequently rats from both groups were sacrificed at 1, 2, and 3 weeks postsurgery. Subchondral bone was evaluated using a high-resolution peripheral quantitative computed tomography scanner, while cartilage was histologically evaluated and scored. Results A significant reduction in the subchondral trabecular bone thickness and spacing was found as early as 1 week postsurgery in ACLT rats compared with the nonoperated control. This was subsequently followed by a reduction in bone mineral density and bone fractional volume at week 2, and finally a decrease in the trabecular number at week 3. These changes occurred together with cartilage degeneration as reflected by an increasing Mankin score over all 3 weeks. Conclusions Significant changes in subchondral bone occur very early in OA concurrent with surface articular cartilage degenerative change suggest that factors affecting bone remodeling and resorption together with cartilage matrix degradation occur very early in the disease.


1998 ◽  
Vol 26 (3) ◽  
pp. 409-414 ◽  
Author(s):  
Darren L. Johnson ◽  
William P. Urban ◽  
David N. M. Caborn ◽  
William J. Vanarthos ◽  
Cathy S. Carlson

Occult osteochondral lesions (bone bruises) have been documented on magnetic resonance images in more than 80% of patients sustaining acute anterior cruciate ligament ruptures. Despite the high prevalence of these lesions, little is known about the histologic changes in the adjacent articular cartilage. Ten patients with acute anterior cruciate ligament ruptures who had a preoperatively documented (by magnetic resonance imaging) geographic bone bruise at the sulcus terminalis on the lateral femoral condyle underwent a 3-mm diameter trephine biopsy of the articular cartilage and subchondral bone overlying the bone bruise at the time of anterior cruciate ligament reconstruction. Biopsy samples of the articular cartilage and subchondral bone were stained with hematoxylin and eosin and toluidine blue. All patients had significant arthroscopic and histologic articular cartilage irregularity in the area overlying the bone bruise. Arthroscopic findings of the articular cartilage included softening (dimpling), fissuring, or overt chondral fracture. Histologic examination revealed degeneration of the chondrocytes and loss of toluidine blue staining in the articular cartilage (loss of proteoglycan). There was necrosis of osteocytes in the subchondral bone, and empty lacuna were visible. This study defines the exact histologic changes of the articular cartilage overlying a geographic bone bruise secondary to an acute anterior cruciate ligament tear. Our findings suggest that a geographic bone bruise found on magnetic resonance imaging indicates substantial damage to normal articular cartilage homeostasis.


2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Li Zeng ◽  
Cai Zhi Xiao ◽  
Zi Ting Deng ◽  
Rong Heng Li

Fu Yuan Capsule (FYC) has been clinically used for osteoarthritis (OA) and its related diseases for many years in China. However, its pharmacological mechanism remains unclear. This study aimed to investigate the potential chondroprotective effects of FYC on articular cartilage. Rat OA model was induced by anterior cruciate ligament transection. A group of rats was treated with FYC for 12 weeks. Joint structure, types I and II collagen, and proteoglycan were evaluated by histological examination. The expression of C-terminal crosslinking telopeptide of type II collagen, hydroxyproline, a disintegrin and metalloproteinase with thrombospondin motifs, matrix metalloproteinase, interleukin-1 beta, nitric oxide, prostaglandin E2, heat-shock protein 70, transforming growth factor-beta, osteoprotegerin, and receptor activator of nuclear factor κB ligand were detected. Treatment with FYC could protect against articular cartilage injury. FYC treatment significantly decreased the extracellular matrix degradation factors and inflammatory mediators. Moreover, articular cartilage protective factors were increased in the FYC group. The current finding suggests that FYC protects articular cartilage in a rat OA model through various ways. Thus, it may be an effective agent for OA treatment.


2017 ◽  
Vol 31 (04) ◽  
pp. 352-358 ◽  
Author(s):  
Chuan He ◽  
Wu He ◽  
Fuke Wang ◽  
Lu Tong ◽  
Zhengguang Zhang ◽  
...  

AbstractThis study aimed to investigate the biomechanical properties of anterior cruciate ligament (ACL); tibial, femoral articular cartilage; and meniscus in knee joints receiving computer-aided or conventional ACL reconstruction. Three-dimensional (3D) knee joint finite element models were established for healthy volunteers (normal group) and patients receiving computer-aided surgery (CAS) or conventional (traditional surgery [TS]) ACL reconstruction. The stress and stress distribution on the ACL, tibial, femoral articular cartilage, and meniscus were examined after force was applied on the 3D knee joint finite element models. No significant differences were observed in the stress on ACL among normal group, CAS group, and TS group when a femoral backward force was loaded. However, when a vertical force of 350 N was loaded on the knee joints, TS group had significant higher stress on the articular cartilage and meniscus than the other two groups at any flexion angle of 0, 30, 60, and 90 degrees. However, no significant differences were observed between CAS group and normal group. In conclusion, computer-aided ACL reconstruction has advantages over conventional surgery approach in restoring the biomechanical properties of knee joints, thus reducing the risk of damage to the knee joint cartilage and meniscus after ACL reconstruction.


2015 ◽  
Vol 75 (9) ◽  
pp. 1714-1721 ◽  
Author(s):  
Zhuang Cui ◽  
Janet Crane ◽  
Hui Xie ◽  
Xin Jin ◽  
Gehua Zhen ◽  
...  

ObjectivesExamine whether osteoarthritis (OA) progression can be delayed by halofuginone in anterior cruciate ligament transection (ACLT) rodent models.Methods3-month-old male C57BL/6J (wild type; WT) mice and Lewis rats were randomised to sham-operated, ACLT-operated, treated with vehicle, or ACLT-operated, treated with halofuginone. Articular cartilage degeneration was graded using the Osteoarthritis Research Society International (OARSI)-modified Mankin criteria. Immunostaining, flow cytometry, RT-PCR and western blot analyses were conducted to detect relative protein and RNA expression. Bone micro CT (μCT) and CT-based microangiography were quantitated to detect alterations of microarchitecture and vasculature in tibial subchondral bone.ResultsHalofuginone attenuated articular cartilage degeneration and subchondral bone deterioration, resulting in substantially lower OARSI scores. Specifically, we found that proteoglycan loss and calcification of articular cartilage were significantly decreased in halofuginone-treated ACLT rodents compared with vehicle-treated ACLT controls. Halofuginone reduced collagen X (Col X), matrix metalloproteinase-13 and A disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS 5) and increased lubricin, collagen II and aggrecan. In parallel, halofuginone-attenuated uncoupled subchondral bone remodelling as defined by reduced subchondral bone tissue volume, lower trabecular pattern factor (Tb.pf) and increased thickness of subchondral bone plate compared with vehicle-treated ACLT controls. We found that halofuginone exerted protective effects in part by suppressing Th17-induced osteoclastic bone resorption, inhibiting Smad2/3-dependent TGF-β signalling to restore coupled bone remodelling and attenuating excessive angiogenesis in subchondral bone.ConclusionsHalofuginone attenuates OA progression by inhibition of subchondral bone TGF-β activity and aberrant angiogenesis as a potential preventive therapy for OA.


2008 ◽  
Vol 36 (10) ◽  
pp. 1966-1977 ◽  
Author(s):  
Eric G. Meyer ◽  
Timothy G. Baumer ◽  
Jill M. Slade ◽  
Walter E. Smith ◽  
Roger C. Haut

Background The knee is one of the most frequently injured joints, including 80 000 anterior cruciate ligament (ACL) tears in the United States each year. Bone bruises are seen in over 80% of patients with ACL injuries, and have been associated with an overt loss of cartilage overlying those regions within 6 months of injury. Hypothesis The level of contact pressure developed in the human knee joint and the extent of articular cartilage and underlying subchondral bone injuries will depend on the mechanism of applied loads/moments during rupture of the ACL. Study Design Controlled laboratory study. Methods Seven knee pairs, flexed to 30°, were loaded in compression or internal torsion until injury. Pressure-sensitive film recorded the magnitude and location of contact. Histologic analysis and magnetic resonance imaging were used to document microtrauma to the tibial plateau cartilage and subchondral bone. Results All specimens suffered ACL injury, either in the form of a midsubstance rupture or avulsion fracture. The contact area and pressures were higher for compression than torsion experiments. After being loaded, the articular cartilage in the central and posterior regions of the medial tibial plateau showed increased magnetic resonance imaging signal intensity, corresponding to an increased susceptibility to absorb water. Histologically, there were more microcracks in the subchondral bone and more articular cartilage damage in the compression than torsion experiments. Conclusion Significant damage occurs to the articular cartilage and underlying subchondral bone during rupture of the ACL. The types and extent of these tissue injuries are a function of the mechanism of ACL rupture. Clinical Relevance Patients suffering an ACL injury may be at risk of osteochondral damage, especially if the mechanism of injury involves a high compressive loading component, such as during a jump landing.


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