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Histopathological changes in the human posterior cruciate ligament during aging and osteoarthritis: correlations with anterior cruciate ligament and cartilage changes.

ABSTRACT: To determine the histological patterns of posterior cruciate ligament (PCL) degeneration during aging and in relation to changes in articular cartilage and anterior cruciate ligament (ACL) across the entire adult age spectrum.Human knee joints (n=120 from 65 donors) were processed within 72 h of postmortem. Articular cartilage surfaces were graded macroscopically. Each PCL was histologically evaluated for inflammation, mucinous changes, chondroid metaplasia, cystic changes and orientation of collagen fibres. The severity of PCL degeneration was classified as normal, mild, moderate or severe. PCL scores were compared to ACL and cartilage scores from the same knees.All knees had intact PCL. Histologically, 6% were normal, 76% showed mild, 12% moderate and 9% severe degeneration. Fibre disorientation was the most prevalent and severe change. Histological grades of PCL and ACL correlated, but significantly fewer PCL than ACL showed severe changes. There was a weaker correlation between aging and total histological PCL scores (R=0.26) compared to aging and ACL scores (R=0.42). ACL scores correlated with cartilage scores (R=0.54) while PCL scores increased with the severity of osteoarthritis from grades 0 to III but not between osteoarthritis grades III-IV (R=0.32). In knees with ruptured ACL, the PCL scores correlated with cartilage scores of the lateral compartment.PCL histopathological changes were less severe than in the ACL. PCL degeneration was associated with ACL and cartilage damage. The lack of correlation with age indicates independent pathways for PCL versus ACL degeneration.

SUBMITTER: Levy YD

PROVIDER: S-EPMC3538921 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature

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Histopathological changes in the human posterior cruciate ligament during aging and osteoarthritis: correlations with anterior cruciate ligament and cartilage changes.

Levy Yadin D YD Hasegawa Akihiko A Patil Shantanu S Koziol James A JA Lotz Martin K MK D'Lima Darryl D DD

Annals of the rheumatic diseases 20120807 2

<h4>Objectives</h4>To determine the histological patterns of posterior cruciate ligament (PCL) degeneration during aging and in relation to changes in articular cartilage and anterior cruciate ligament (ACL) across the entire adult age spectrum.<h4>Methods</h4>Human knee joints (n=120 from 65 donors) were processed within 72 h of postmortem. Articular cartilage surfaces were graded macroscopically. Each PCL was histologically evaluated for inflammation, mucinous changes, chondroid metaplasia, cy ...[more]

PMID: 22872023

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Project description:BackgroundOsteoarthritis (OA) is a debilitating, progressive joint disease.MethodsSimilar to the disease progression in humans, sequential events of early cartilage degradation, subchondral osteopenia followed by sclerosis, and late osteophyte formation were demonstrated in the anterior cruciate ligament transection (ACLT) or ACLT with partial medial meniscectomy (ACLT + MMx) rat OA models. We describe a reliable and consistent method to examine the time dependent changes in the gene expression profiles in articular cartilage and subchondral bone.ResultsLocal regulation of matrix degradation markers was demonstrated by a significant increase in mRNA levels of aggrecanase-1 and MMP-13 as early as the first week post-surgery, and expression remained elevated throughout the 10 week study. Immunohistochemistry confirmed MMP-13 expression in differentiated chondrocytes and synovial fibroblasts at week-2 and cells within osteophytes at week-10 in the surgically-modified-joints. Concomitant increases in chondrocyte differentiation markers, Col IIA and Sox 9, and vascular invasion markers, VEGF and CD31, peaked around week-2 to -4, and returned to Sham levels at later time points in both models. Indeed, VEGF-positive cells were found in the deep articular chondrocytes adjacent to subchondral bone. Osteoclastic bone resorption markers, cathepsin K and TRAP, were also elevated at week-2. Confirming bone resorption is an early local event in OA progression, cathepsin K positive osteoclasts were found invading the articular cartilage from the subchondral region at week 2. This was followed by late disease events, including subchondral sclerosis and osteophyte formation, as demonstrated by the upregulation of the osteoanabolic markers runx2 and osterix, toward week-4 to 6 post-surgery.ConclusionsIn summary, this study demonstrated the temporal and cohesive gene expression changes in articular cartilage and subchondral bone using known markers of OA progression. The findings here support genome-wide profiling efforts to elucidate the sequential and complex regulation of the disease.

Project description:BackgroundWe aimed to evaluate clinical and radiological results after simultaneous open-wedge high tibial osteotomy (HTO) and anterior cruciate ligament (ACL) reconstruction in patients with ACL deficiency combined with medial uni-compartmental osteoarthritis (OA) and varus deformity.MethodsThis retrospective study was performed using data collected from 2005 to 2011 on a total of 24 patients who were diagnosed with ACL injury and medial unicompartmental OA with varus deformity, and who subsequently underwent simultaneous open-wedge HTO and arthroscopic ACL reconstruction. The mean follow-up duration was 5.2 years. For clinical outcomes, we evaluated Lysholm score, Tegner activity score, range of motion, Lachmann test, and pivot-shift test, and for radiological outcomes, we evaluated the degree of varus deformity, progression of medial OA, tibial posterior slope, anterior instability, and postoperative complication.ResultsThere were no limitations in range of motion found in any cases. Three patients showed progressive osteoarthritis on the medial compartment. The mechanical femorotibial angle was significantly corrected from varus 7.0 degrees to valgus 1.2 degrees, and the tibial posterior slope was not significantly changed. The Lysholm and Tegner activity scores were significantly improved after surgery (from 58 to 94 points on the Lysholm scale and from 4.0 to 5.3 points on the Tegner activity scale). Although the Lachman test and the pivot-shift test showed significant improvements after surgery, instability greater than Gr II was observed in three patients on the Lachman test and in four patients on the pivot-shift test. The side-to-side difference improved from 9.6 mm to 4.2 mm postoperatively as assessed using a Telos® arthrometer. There were no cases of nonunion or fixation loss.ConclusionsSimultaneous open-wedge HTO and ACL reconstruction in patients with ACL injury with medial compartmental OA showed satisfactory functional outcomes and postoperative activity level scores. However, some patients showed residual instability and progression of OA.

Project description:BackgroundDegeneration of the tibiofemoral articular cartilage often develops in patients with posterior cruciate ligament deficiency, yet little research has focused on the etiology of this specific type of cartilage degeneration. In this study, we hypothesized that posterior cruciate ligament deficiency changes the location and magnitude of cartilage deformation in the tibiofemoral joint.MethodsFourteen patients with a posterior cruciate ligament injury in one knee and the contralateral side intact participated in the study. First, both knees were imaged with use of a specific magnetic resonance imaging sequence to create three-dimensional knee models of the surfaces of the bone and cartilage. Next, each patient performed a single leg lunge as images were recorded with a dual fluoroscopic system at 0 degrees, 30 degrees, 60 degrees, 75 degrees, 90 degrees, 105 degrees, and 120 degrees of knee flexion. Finally, the three-dimensional knee models and fluoroscopic images were used to reproduce the in vivo knee position at each flexion angle with use of a previously described image-matching method. With use of these series of knee models, the location and magnitude of peak tibiofemoral cartilage deformation at each flexion angle were compared between the intact contralateral and posterior cruciate ligament-deficient knees.ResultsIn the medial compartment of the posterior cruciate ligament-deficient knees, the location and magnitude of peak cartilage deformation were significantly changed, compared with those in the intact contralateral knees, between 75 degrees and 120 degrees of flexion, with a more anterior and medial location of peak cartilage deformation on the tibial plateau as well as increased deformation of the cartilage. In the lateral compartment, no significant differences in the location or magnitude of peak cartilage deformation were found between the intact and posterior cruciate ligament-deficient knees.ConclusionsThe altered kinematics associated with posterior cruciate ligament deficiency resulted in a shift of the tibiofemoral contact location and an increase in cartilage deformation in the medial compartment beyond 75 degrees of knee flexion. The magnitude of the medial contact shift in the posterior cruciate ligament-deficient knee was on the same order as that of the anterior contact shift.

Project description:ObjectiveTo investigate the mitigate efficacy of Chinese medicine Lingzhi (LZ) and San-Miao-San (SMS) combined with hyaluronic acid (HA)-gel in attenuating cartilage degeneration in traumatic osteoarthritis (OA).MethodsThe standardized surgery of anterior cruciate ligament transection (ACLT) was made from the medial compartment of right hind limbs of 8-week-old female SD rats and resulted in a traumatic OA. Rats (n = 5/group) were treated once intra-articular injection of 50 μl HA-gel, 50 μl HA-gel+50 μg LZ-SMS, 50 μl of saline+50 μg LZ-SMS and null (ACLT group) respectively, except sham group. Limbs were harvested for μCT scan and histopathological staining 3-month post-treatment. Inflammatory cytokines from plasma and synovial fluid were detected using Immunology Multiplex Assay kit. The putative targets of active compounds in LZ-SMS and known therapeutic targets for OA were combined to construct protein-protein interaction network. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was adopted to predict the potential targets and signaling pathway of LZ-SMS in OA through the tool of DAVID Bioinformatics.ResultsIn vivo, HA-gel + LZ-SMS treatment resulted in a higher volume ratio of hyaline cartilage (HC)/calcified cartilage (CC) and HC/Sum (total volume of cartilage), compared to ACLT and HA-gel groups. In addition, histological results showed the elevated cartilage matrix, chondrogenic and osteoblastic signals in HA-gel + LZ-SMS treatment. Treatment also significantly altered subchondral bone (SCB) structure including an increase in BV/TV, Tb.Th, BMD, Conn.Dn, Tb.N, and DA, as well as a significant decrease in Tb.Sp and Po(tot), which implied a protective effect on maintaining the stabilization of tibial SCB microstructure. Furthermore, there was also a down-regulated inflammatory cytokines and upregulated anti-inflammatory cytokine IL-10 in HA+LZ-SMS group. Finally, 64 shared targets from 37 active compounds in LZ-SMS related to the core genes for the development of OA. LZ-SMS has a putative role in regulating inflammatory circumstance through influencing the MAPK signaling pathway.ConclusionOur study elucidated a protective effect of HA-gel + LZ-SMS in mitigating cartilage degradation and putative interaction with targets and signaling pathway for the development of traumatic OA.The translational potential of this articleOur results provide a biological rationale for the use of LZ-SMS as a potential candidate for OA treatment.

Dataset Information

Histopathological changes in the human posterior cruciate ligament during aging and osteoarthritis: correlations with anterior cruciate ligament and cartilage changes.

Publications

Histopathological changes in the human posterior cruciate ligament during aging and osteoarthritis: correlations with anterior cruciate ligament and cartilage changes.

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