Cartilage Matrix Degeneration Occurs within the First Year after ACLR and Is Associated with Impaired Clinical Outcome

Objective Anterior cruciate ligament reconstruction (ACLR) has not been shown to decrease the risk for development of post-traumatic osteoarthritis. Magnetic resonance imaging (MRI) T2 mapping can be used to assess cartilage compositional changes. This study tests whether (1) worse cartilage arthroscopic status at ACLR is reflected by higher cartilage T2 values in matched study regions 6 weeks and 1 year after ACLR, and (2) increasing cartilage T2 values between 6 weeks and 1 year after ACLR are associated with worsening patient-reported outcomes. Design Twenty-two participants with ACLR and 26 controls underwent 3T MRI. T2 values in medial and lateral femoral and tibial cartilage were measured at 6 weeks and 1 year after ACLR and compared with arthroscopic grades, Knee injury and Osteoarthritis Outcome Scores (KOOS), and control T2 values. Results Most (59%-86%) cartilage study regions examined by arthroscopy demonstrated intact articular surfaces. Average T2 value increased in 3 of 4 study regions between 6 weeks and 1 year after ACLR ( P = .001-.011). T2 value increased ( P < .013) even for participants whose cartilage had intact articular surfaces at ACLR. Participants with ACLR who showed greater increases in cartilage T2 values had less improvement to KOOS Quality of Life ( P = .009, ρ = −0.62). Discussion Cartilage status assessed arthroscopically at ACLR and by MRI T2 maps 6 weeks later was healthier than cartilage status assessed by MRI T2 maps at 1-year follow-up. Progressive T2 elevations were observed over the first year after ACLR even in patients with arthroscopically intact cartilage at the time of surgery and were associated with reduced improvement in knee quality of life suggesting preosteoarthritis.

Ultrasound-Based Quantification of Cartilage Damage After In Vivo Articulation With Metal Implants

Objective This study aims to evaluate the applicability of the ultrasound roughness index (URI) for quantitative assessment of cartilage quality ex vivo (post-mortem), after 6 months of in vivo articulation with a Focal Knee Resurfacing Implant (FKRI). Design Goats received a metal FKRI ( n = 8) or sham surgery ( n = 8) in the medial femoral condyles. After 6 months animals were sacrificed, tibial plateaus were stained with Indian ink, and macroscopic scoring of the plateaus was performed based on the ink staining. The URI was calculated from high-frequency ultrasound images at several sections, covering both areas that articulated with the implant and non-articulating areas. Cartilage quality at the most damaged medial location was evaluated with a Modified Mankin Score (MMS). Results The URI was significantly higher in the FKRI-articulating than in the sham plateaus at medial articulating sections, but not at sections that were not in direct contact with the implant, for example, under the meniscus. The mean macroscopic score and MMS were significantly higher in the FKRI-articulating group than in the sham group ([Formula: see text], [Formula: see text], respectively). Correlation coefficients between URI and macroscopic score were significant in medial areas that articulated with the implant. A significant correlation between URI and MMS was found at the most damaged medial location ([Formula: see text]). Conclusions This study demonstrates the potential of URI to evaluate cartilage roughness and altered surface morphology after in vivo articulation with a metal FKRI, rendering it a promising future tool for quantitative follow-up assessment of cartilage quality.

Role of Mitochondria in Physiology of Chondrocytes and Diseases of Osteoarthritis and Rheumatoid Arthritis

Purpose of Review Mitochondria are recognized to be one of the most important organelles in chondrocytes for their role in triphosphate (ATP) generation through aerobic phosphorylation. Mitochondria also participate in many intracellular processes involving modulating reactive oxygen species (ROS), responding to instantaneous hypoxia stress, regulating cytoplasmic transport of calcium ion, and directing mitophagy to maintain the homeostasis of individual chondrocytes. Designs To summarize the specific role of mitochondria in chondrocytes, we screened related papers in PubMed database and the search strategy is ((mitochondria) AND (chondrocyte)) AND (English [Language]). The articles published in the past 5 years were included and 130 papers were studied. Results In recent years, the integrity of mitochondrial structure has been regarded as a prerequisite for normal chondrocyte survival and defect in mitochondrial function has been found in cartilage-related diseases, such as osteoarthritis (OA) and rheumatoid arthritis (RA). However, the understanding of mitochondria in cartilage is still largely limited. The mechanism on how the changes in mitochondrial structure and function directly lead to the occurrence and development of cartilage-related diseases remains to be elusive. Conclusion This review aims to summarize the role of mitochondria in chondrocytes under the physiological and pathological changes from ATP generation, calcium homeostasis, redox regulation, mitophagy modulation, mitochondria biogenesis to immune response activation. The enhanced understanding of molecular mechanisms in mitochondria might offer some new cues for cartilage remodeling and pathological intervention.

Time Matters: Knee Cartilage Defect Expansion and High-Grade Lesion Formation while Awaiting Autologous Chondrocyte Implantation

Objective The objective of this study was to assess potential risk factors, including time delay until implantation, for knee cartilage defect expansion or new high-grade defect formation between biopsy and Autologous Chondrocyte Implantation (ACI) or Matrix Autologous Chondrocyte Implantation (MACI). Study design Consecutive knee ACI and MACI cases by a single surgeon ( n = 111) were reviewed. The relationship between time between biopsy and staged implantation and (1) progression in primary cartilage defect size and (2) development of a new high-grade (Outerbridge grade ≥3) cartilage defect were determined with adjustment for demographics, body mass index, smoking status, coronal alignment, initial cartilage status, and prior surgery. Results Average size of the primary defect at time of biopsy was 4.50 cm2. Mean time to chondrocyte implantation was 155 days. Defect expansion increased 0.11 cm2 (standard error = 0.03) per month delay to implantation ( P = 0.001). Independent predictors of defect expansion were male sex, smaller initial defect size, and delay to implantation (adjusted mean = 0.15 cm2 expansion per month). A total of 16.2% of patients ( n = 18/111) developed a new high-grade defect. Independent predictors of a new secondary defect were Outerbridge grade 2 changes (vs. 0-1) on the surface opposing the index defect and delayed implantation (per month increase, adjusted odds ratio = 1.21, 95% confidence interval: 1.01-1.44; P = 0.036). Conclusions Patients undergoing 2-stage cell-based cartilage restoration with either ACI or MACI demonstrated long delays between stages of surgery, placing them at risk for expanding defects and development of new high-grade cartilage defects. Patients who were male, had smaller initial defect size, and longer time between surgeries were at greater risk for defect expansion. Level of Evidence III, retrospective comparative study.

Physiological Reloading Recovers Histologically Disuse Atrophy of the Articular Cartilage and Bone by Hindlimb Suspension in Rat Knee Joint

Objective This study aimed to clarify physiological reloading on disuse atrophy of the articular cartilage and bone in the rat knee using the hindlimb suspension model. Design Thirty male rats were divided into 3 experimental groups: control group, hindlimb suspension group, and reloading after hindlimb suspension group. Histological changes in the articular cartilage and bone of the tibia were evaluated by histomorphometrical and immunohistochemical analyses at 2 and 4 weeks after reloading. Results The thinning and loss of matrix staining in the articular cartilage and the decrease in bone volume induced by hindlimb suspension recovered to the same level as the control group after 2 weeks of reloading. The proportion of the noncalcified and calcified layers of the articular cartilage and the thinning of subchondral bone recovered to the same level as the control group after 4 weeks of reloading. Conclusions Disuse atrophy of the articular cartilage and bone induced by hindlimb suspension in the tibia of rats was improved by physiological reloading.

Treating Full Depth Cartilage Defects with Intraosseous Infiltration of Plasma Rich in Growth Factors: An Experimental Study in Rabbits

Objective Intraarticular (IA) administration of platelet-rich plasma (PRP) has been proposed as a new strategy to halt osteoarthritis (OA) progression. In patients with severe OA, its potential is limited because it is unable to reach the subchondral bone, so a new strategy is needed, and intraosseous (IO) infiltration has been suggested. The purpose is to assess the impact of IA together with IO infiltration of plasma rich in growth factors (PRGF) in serum hyaluronic acid (HA) and type II collagen cleavage neoepitope (C2C) levels. Design A total of 32 rabbits were included in the study and randomly divided into 2 groups: control and treatment. A 4-mm chondral defect was created in the medial femoral condyle and IA followed by IO infiltration were performed. Serum C2C and HA levels were measured using enzyme-linked immunosorbent assay (ELISA) tests before infiltration and 28, 56, and 84 days post-infiltration. Results Significant lower C2C serum levels were obtained in treatment group (IA + IO infiltration of PRGF) at 84 days post-infiltration than in control group (IA infiltration of PRGF + IO infiltration of saline solution), while no significant differences between groups were reported at any other study times. Regarding HA, at 56 days post-infiltration, greater significant levels were seen in the treatment group. However, at 84 days post-infiltration, no significant differences were obtained, although lower levels were reported in the treatment group. Conclusions Despite inconclusive, the results suggest that the combination of IA and IO infiltration with PRGF may enhance cartilage and subchondral bone regeneration, but further studies are needed.

Infrared Thermography for the Evaluation of Inflammatory and Degenerative Joint Diseases: A Systematic Review

Objective Inflammation plays a central role in the pathophysiology of rheumatic diseases as well as in osteoarthritis. Temperature, which can be quantified using infrared thermography, provides information about the inflammatory component of joint diseases. This systematic review aims at assessing infrared thermography potential and limitations in these pathologies. Design A systematic review was performed on 3 major databases: PubMed, Cochrane library, and Web of Science, on clinical reports of any level of evidence in English language, published from 1990 to May 2021, with infrared thermography used for diagnosis of osteoarthritis and rheumatic diseases, monitoring disease progression, or response to treatment. Relevant data were extracted, collected in a database, and analyzed for the purpose of this systematic review. Results Of 718 screened articles 32 were found to be eligible for inclusion, for a total of 2094 patients. Nine studies reported the application to osteoarthritis, 21 to rheumatic diseases, 2 on both. The publication trend showed an increasing interest in the last decade. Seven studies investigated the correlation of temperature changes with osteoarthritis, 16 with rheumatic diseases, and 2 with both, whereas 2 focused on the pre-post evaluation to investigate treatment results in patients with osteoarthritis and 5 in patients with rheumatic diseases. A correlation was shown between thermal findings and disease presence and stage, as well as the clinical assessment of disease activity and response to treatment, supporting infrared thermography role in the study and management of rheumatic diseases and osteoarthritis. Conclusions The systematic literature review showed an increasing interest in this technology, with several applications in different joints affected by inflammatory and degenerative pathologies. Infrared thermography proved to be a simple, accurate, noninvasive, and radiation-free method, which could be used in addition to the currently available tools for screening, diagnosis, monitoring of disease progression, and response to medical treatment.

Anterior Cruciate Ligament Reconstruction versus Nonoperative Treatment: Better Function and Less Secondary Meniscectomies But No Difference in Knee Osteoarthritis—A Meta-Analysis

Objectives The impact of anterior cruciate ligament (ACL) reconstruction on knee osteoarthritis (OA) is still unclear. The aim of the current meta-analysis was to compare surgical treatment versus nonoperative management of ACL tears to assess the impact of these approaches on knee OA development at a 5 and 10 years of follow-up. Design A meta-analysis was performed after a systematic literature search (May 2021) was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. Both randomized and nonrandomized comparative studies with more than 5 years of follow-up were selected. Influence of the treatment was assessed in terms of knee OA development, subjective and objective clinical results, activity level, and risk of further surgeries. Risk of bias and quality of evidence were assessed following the Cochrane guidelines. Results Twelve studies matched the inclusion criteria, for a total of 1,004 patients. Level of evidence was rated low to very low. No difference was documented in terms of knee OA development, Tegner score, subjective International Knee Documentation Committee (IKDC), and Lysholm scores. A significant difference favoring the surgical treatment in comparison with a nonsurgical approach was observed in terms of objective IKDC score ( P = 0.03) and risk of secondary meniscectomy ( P < 0.0001). The level of evidence was considered very low for subjective IKDC, low for knee OA development, objective IKDC, number of secondary meniscectomies, and Lysholm score, and moderate for post-op Tegner score. Conclusions The meta-analysis did not support an advantage of ACL reconstruction in terms of OA prevention in comparison with a nonoperative treatment. Moreover, no differences were reported for subjective results and activity level at 5 and 10 years of follow-up. On the contrary, patients who underwent surgical treatment of their ACL tear presented important clinical findings in terms of better objective knee function and a lower rate of secondary meniscectomies when compared with conservatively managed patents. Protocol Registration: CRD420191156483 (PROSPERO)

Methodology to Quantify Collagen Subtypes and Crosslinks: Application in Minipig Cartilages

Introduction This study develops assays to quantify collagen subtypes and crosslinks with liquid chromatography-mass spectrometry (LC-MS) and characterizes the cartilages in the Yucatan minipig. Methods For collagen subtyping, liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis was performed on tissues digested in trypsin. For collagen crosslinks, LC-MS analysis was performed on hydrolysates. Samples were also examined histologically and with bottom-up proteomics. Ten cartilages (femoral condyle, femoral head, facet joint, floating rib, true rib, auricular cartilage, annulus fibrosus, 2 meniscus locations, and temporomandibular joint disc) were analyzed. Results The collagen subtyping assay quantified collagen types I and II. The collagen crosslinks assay quantified mature and immature crosslinks. Collagen subtyping revealed that collagen type I predominates in fibrocartilages and collagen type II in hyaline cartilages, as expected. Elastic cartilage and fibrocartilages had more mature collagen crosslink profiles than hyaline cartilages. Bottom-up proteomics revealed a spectrum of ratios between collagen types I and II, and quantified 42 proteins, including 24 collagen alpha-chains and 12 minor collagen types. Discussion The novel assays developed in this work are sensitive, inexpensive, and use a low operator time relative to other collagen analysis methods. Unlike the current collagen assays, these assays quantify collagen subtypes and crosslinks without an antibody-based approach or lengthy chromatography. They apply to any collagenous tissue, with broad applications in tissue characterization and tissue engineering. For example, a novel finding of this work was the presence of a large quantity of collagen type III in the white-white knee meniscus and a spectrum of hyaline and fibrous cartilages.

7-Tesla MRI Evaluation of the Knee, 25 Years after Cartilage Repair Surgery: The Influence of Intralesional Osteophytes on Biochemical Quality of Cartilage

Objective To evaluate the morphological and biochemical quality of cartilage transplants and surrounding articular cartilage of patients 25 years after perichondrium transplantation (PT) and autologous chondrocyte transplantation (ACT) as measured by ultra-high-field 7-Tesla (7T) magnetic resonance imaging (MRI) and to present these findings next to clinical outcome. Design Seven PT patients and 5 ACT patients who underwent surgery on the femoral condyle between 1986 and 1996 were included. Patient-reported outcome measures (PROMs) were assessed by the clinical questionnaires: Knee injury and Osteoarthritis Outcome Score (KOOS), International Knee Documentation Committee (IKDC), and Visual Analogue Scale (VAS) for knee pain. The morphological (MOCART score) and biochemical quality (glycosaminoglycans [GAGs] content and collagen integrity) of cartilage transplants and surrounding articular cartilage were analyzed by 7T MRI. The results of the PT and ACT patients were compared. Finally, a detailed morphological analysis of the grafts alone was performed. Results No statistically significant difference was found for the PROMs and MOCART scores of PT and ACT patients. Evaluation of the graft alone showed poor repair tissue quality and high prevalence of intralesional osteophyte formation in both the PT and ACT patients. Penetration of the graft surface by the intralesional osteophyte was related to biochemically damaged opposing tibial cartilage; GAG content was significantly lower in patients with an osteophyte penetrating the graft surface. Conclusions Both PT and ACT patients have a high incidence of intralesional osteophyte formation 25 years after surgery. The resulting biochemical damage to the opposing tibial cartilage might be dependent on osteophyte morphology.