Osteoarthritis (OA) is a degenerative disease resulting from progressive joint destruction caused by many factors. Its pathogenesis is complex and has not been elucidated to date. Advanced glycation end products (AGEs) are a series of irreversible and stable macromolecular complexes formed by reducing sugar with protein, lipid, and nucleic acid through a non-enzymatic glycosylation reaction (Maillard reaction). They are an important indicator of the degree of ageing. Currently, it is considered that AGEs accumulation in vivo is a molecular basis of age-induced OA, and AGEs production and accumulation in vivo is one of the important reasons for the induction and acceleration of the pathological changes of OA. In recent years, it has been found that AGEs are involved in a variety of pathological processes of OA, including extracellular matrix degradation, chondrocyte apoptosis, and autophagy. Clearly, AGEs play an important role in regulating the expression of OA-related genes and maintaining the chondrocyte phenotype and the stability of the intra-articular environment. This article reviews the latest research results of AGEs in a variety of pathological processes of OA, to provide a new direction for the study of OA pathogenesis and a new target for prevention and treatment.

Cite this article: Bone Joint Res 2022;11(5):292–300.

Treatment for osteoarthritis (OA) has traditionally focused on joint replacement for end-stage disease. An increasing number of surgical and pharmaceutical strategies for disease prevention have now been proposed. However, these require the ability to identify OA at a stage when it is potentially reversible, and detect small changes in cartilage structure and function to enable treatment efficacy to be evaluated within an acceptable timeframe. This has not been possible using conventional imaging techniques but recent advances in musculoskeletal imaging have been significant. In this review we discuss the role of different imaging modalities in the diagnosis of the earliest changes of OA. The increasing number of MRI sequences that are able to non-invasively detect biochemical changes in cartilage that precede structural damage may offer a great advance in the diagnosis and treatment of this debilitating condition. Cite this article: Bone Joint J 2013;95-B:738–46

Recently, femoroacetabular impingement has been recognised as a cause of early osteoarthritis. There are two mechanisms of impingement: 1) cam impingement caused by a non-spherical head and 2) pincer impingement caused by excessive acetabular cover. We hypothesised that both mechanisms result in different patterns of articular damage. Of 302 analysed hips only 26 had an isolated cam and 16 an isolated pincer impingement. Cam impingement caused damage to the anterosuperior acetabular cartilage with separation between the labrum and cartilage. During flexion, the cartilage was sheared off the bone by the non-spherical femoral head while the labrum remained untouched. In pincer impingement, the cartilage damage was located circumferentially and included only a narrow strip. During movement the labrum is crushed between the acetabular rim and the femoral neck causing degeneration and ossification. Both cam and pincer impingement lead to osteoarthritis of the hip. Labral damage indicates ongoing impingement and rarely occurs alone

Aims

Circular RNA (circRNA) is involved in the regulation of articular cartilage degeneration induced by inflammatory factors or oxidative stress. In a previous study, we found that the expression of circStrn3 was significantly reduced in chondrocytes of osteoarthritis (OA) patients and OA mice. Therefore, the aim of this paper was to explore the role and mechanism of circStrn3 in osteoarthritis.

1. A case of discoid medial cartilage is describe—the fifth so far recorded—and comparison is made with the previous cases in the literature. 2. The origin of the anomaly, its incidence and clinical features are discussed. 3. The view is expressed that discoid cartilage is a congenital lesion due to abnormal development, fibrocartilage being laid down in mesenchyme which normally disappears in the formation of the joint. It is not the effect of arrest of a normal process or persistence of a normal foetal state. The only time at which a cartilage may be said to be disc-shaped is in the earliest weeks of embryonic life, when the disc or plaque of undifferentiated mesenchyme is present between the developing bones. The central part of this mass disappears early, and the fibrocartilage develops in its peripheral portion. In a ten-weeks'-old embryo (37 millimetres) the cartilages were shown to have a crescentic shape like that of the adult cartilage

This study relates the extent of cartilage lesions within the first metatarsophalangeal joint to hallux valgus. We prospectively examined 265 first metatarsophalangeal joints of 196 patients with a mean age of 54.2 years at operation for the existence of cartilage lesions. Grade I lesions were found in 41 feet (15.5%), grade II in 82 (30.9%), grade III in 51 (19.3%), grade IV in 20 (7.5%). Only 71 (26.8%) showed no cartilage lesion. Cartilage lesions were found within the metatarsosesamoid and metatarsophalangeal compartments in 66 feet (34.0%), within the metatarsophalangeal compartment in 26 (13.4%) and within the metatarsosesamoid compartment in 102 (52.6%). A statistically significant correlation was found between the grade of cartilage lesion and the hallux valgus angle, both for the changes within the metatarsophalangeal and the metatarsosesamoid joints

1. An experimental technique for the transplantation of epiphysial cartilage in the rabbit is described. 2. Autogenous transposition of the distal epiphysial cartilage of the ulna was followed by normal growth in five of eighteen animals. 3. Homogenous transplantation was unsuccessful in all the animals studied. 4. Homogenous grafting gives rise to an immunity reaction confined to the reserve Zone of the cartilage. 5. It is suggested that the difference between the fate of homogenous grafts of epiphysial and non-epiphysial cartilage lies in the vascularity of the former

We compared the quality of debridement of chondral lesions performed by four arthroscopic (SH, shaver; CU, curette; SHCU, shaver and curette; BP, bipolar electrodes) and one open technique (OPEN, scalpel and curette) which are used prior to autologous chondrocyte implantation (ACI). The ex vivo simulation of all five techniques was carried out on six juvenile equine stifle joints. The OPEN, SH and SHCU techniques were tested on knees harvested from six adult human cadavers. The most vertical walls with the least adjacent damage to cartilage were obtained with the OPEN technique. The CU and SHCU methods gave inferior, but still acceptable results whereas the SH technique alone resulted in a crater-like defect and the BP method undermined the cartilage wall. The subchondral bone was severely violated in all the equine samples which might have been peculiar to this model. The predominant depth of the debridement in the adult human samples was at the level of the calcified cartilage. Some minor penetrations of the subchondral end-plate were induced regardless of the instrumentation used. Our study suggests that not all routine arthroscopic instruments are suitable for the preparation of a defect for ACI. We have shown that the preferred debridement technique is either open or arthroscopically-assisted manual curettage. The use of juvenile equine stifles was not appropriate for the study of the cartilage-subchondral bone interface

Objectives. Matrix-assisted autologous chondrocyte transplantation (MACT) has been developed and applied in the clinical practice in the last decade to overcome most of the disadvantages of the first generation procedures. The purpose of this systematic review is to document and analyse the available literature on the results of MACT in the treatment of chondral and osteochondral lesions of the knee. Methods. All studies published in English addressing MACT procedures were identified, including those that fulfilled the following criteria: 1) level I-IV evidence, 2) measures of functional or clinical outcome, 3) outcome related to cartilage lesions of the knee cartilage. Results. The literature analysis showed a progressively increasing number of articles per year. A total of 51 articles were selected: three randomised studies, ten comparative studies, 33 case series and five case reports. Several scaffolds have been developed and studied, with good results reported at short to medium follow-up. Conclusions. MACT procedures are a therapeutic option for the treatment of chondral lesions that can offer a positive outcome over time for specific patient categories, but high-level studies are lacking. Systematic long-term evaluation of these techniques and randomised controlled trials are necessary to confirm the potential of this treatment approach, especially when comparing against less ambitious traditional treatments

1. The semilunar cartilages are part of the rotator mechanism of the knee joint. 2. Movement of the weight-bearing knee comprises synchronous lateral rotation of the tibia with extension and medial rotation of the tibia with flexion. 3. When this synchrony is disturbed, injuries to the semilunar cartilages result. 4. Damage to the anterior two-thirds of the medial cartilage blocks lateral rotation of the tibia, with consequent physical signs that are pathognomonic of the retracted and the bowstring cartilage, which are the most common types of injury. 5. Each type of cartilage injury produces its own pattern of erosion of articular cartilage and its own sequence of symptoms as so-called arthritis develops. 6. The sequence of symptoms may be halted and often reversed by removal of the torn cartilage. Operation is warranted in most cases however long the history and whatever the age of the patient. 7. The development of medial retropatellar arthritis is explained. The symptoms are often relieved by removal of the medial semilunar cartilage and adequate post-operative rehabilitation

1. Isografts of articular cartilage of young rats, with mucoproteins labelled with . 35. S, extracellular fibrous proteins labelled with . 3. H-glycine, and nuclei labelled with . 3. H-thymidine, were transplanted into the anterior chamber of the eye. 2. Thin split-thickness transplants of the cells of the gliding surface of immature articular cartilage induced the formation of fibrous tissue. 3. Thick transplants and subsurface slices of immature articular cartilage, containing germinal cells of the epiphysial cartilage, induced the formation of new bone consistently within 4 weeks. 4. Full-thickness transplants in articular cartilage from senile rats induced only the formation of fibrous tissue. 5. Slices of growing cartilage, devitalised by cryolysis, or extraction of acid-soluble proteins, produced scanty deposits of bone or cartilage, or both, but only infrequently and generally after a lag phase extending from six to twelve weeks. 6. Reduction in the amount of mucoprotein in the cartilage matrix by papain, and suppression of the resynthesis of tissue proteins by cortisone, retarded but did not prevent bone induction. 7. Bone induction is the product of a series of interactions between inducing cells and responding cells by intracellular and intercellular reactions too complex to characterise in physico-chemical terms at this time

1. Stable strontium in large amount in the diet of rats initially inhibits calcification and induces rickets. 2. Changes later become atypical and a complex series of epiphysial plate defects develops: formation of localised osteoid wedges in the metaphysis; invagination of the epiphysial plate and sequestration of multiple cartilage nodules into the marrow cavity; and, in severely affected animals, localised loss of part or parts of the epiphysial plate with formation of large cartilage nodules in the metaphysis and epiphysis. 3. The appearance of cartilage nodules in the metaphysis in man has been shown to be associated with changes in the epiphysial plate, but much of the information is radiological and therefore incomplete, and detailed cellular changes are seldom available. 4. Some of the conditions mentioned, which have presented difficulty in interpretation, partly because of their rarity but also because of lack of knowledge of the fundamental processes concerned, are multiple exostoses and endochondromatoses, metaphysial dysostosis and osteochondritis. 5. Comparison of basic mechanisms revealed in this study with those supposed to occur in human cartilage dystrophies demonstrates that strontium rickets mimics some changes occurring in chronic renal rickets; that invagination of the epiphysial plate and cartilage nodule sequestration could account for the development of multiple exostoses and some endochondromatoses; and that localised endochondral defects in calcification can induce epiphysial changes resembling osteochondritis juvenilis, demonstrating that avascular necrosis is not necessarily the mechanism initiating epiphysial deformity

Infection of human cartilage with HIV in vivo has not previously been reported. Specimens of articular cartilage taken at postmortem from ten patients who were HIV-positive were examined. Two had AIDS and eight were believed to have stage-2 disease. The standard polymerase chain reaction (PCR) protocol was modified to allow semiquantitative analysis of the samples. Oligonucleotide primers labelled with . 32. P gamma-ATP were used to detect a segment of HIV DNA and a control DNA gene segment (HLA genome) to estimate the ratio of infected cells. The . 32. P-labelled PCR products were separated on acrylamide gels and visualised directly by autoradiography and computer densitometry. Infection of human cartilage in vivo was demonstrated in nine of the ten samples in which the PCR analysis was positive. The other did not react sufficiently to produce detectable radiolabelled PCR product despite repeated DNA digestion and extraction. Cartilage infected with HIV could be a potential source of HIV when used in operations

Gene therapy with insulin-like growth factor-1 (IGF-1) increases matrix production and enhances chondrocyte proliferation and survival in vitro. The purpose of this study was to determine whether arthroscopically-grafted chondrocytes genetically modified by an adenovirus vector encoding equine IGF-1 (AdIGF-1) would have a beneficial effect on cartilage healing in an equine femoropatellar joint model. A total of 16 horses underwent arthroscopic repair of a single 15 mm cartilage defect in each femoropatellar joint. One joint received 2 × 10. 7. AdIGF-1 modified chondrocytes and the contralateral joint received 2 × 10. 7. naive (unmodified) chondrocytes. Repairs were analysed at four weeks, nine weeks and eight months after surgery. Morphological and histological appearance, IGF-1 and collagen type II gene expression (polymerase chain reaction, in situ hybridisation and immunohistochemistry), collagen type II content (cyanogen bromide and sodium dodecyl sulphate-polyacrylamide gel electrophoresis), proteoglycan content (dimethylmethylene blue assay), and gene expression for collagen type I, matrix metalloproteinase (MMP)-1, MMP-3, MMP-13, aggrecanase-1, tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) and TIMP-3 were evaluated. Genetic modification of chondrocytes significantly increased IGF-1 mRNA and ligand production in repair tissue for up to nine weeks following transplantation. The gross and histological appearance of IGF-1 modified repair tissue was improved over control defects. Gross filling of defects was significantly improved at four weeks, and a more hyaline-like tissue covered the lesions at eight months. Histological outcome at four and nine weeks post-transplantation revealed greater tissue filling of defects transplanted with genetically modified chondrocytes, whereas repair tissue in control defects was thin and irregular and more fibrous. Collagen type II expression in IGF-1 gene-transduced defects was increased 100-fold at four weeks and correlated with increased collagen type II immunoreaction up to eight months. Genetic modification of chondrocytes with AdIGF-1 prior to transplantation improved early (four to nine weeks), and to a lesser degree long-term, cartilage healing in the equine model. The equine model of cartilage healing closely resembles human clinical cartilage repair. The results of this study suggest that cartilage healing can be enhanced through genetic modification of chondrocytes prior to transplantation

1. The hypothesis is put forward that the cartilage of a developing epiphysis consists of two separate moieties. There is a superficial zone which from the first is destined to become articular cartilage and is incapable of ossification, whereas the deeper layers are concerned with the actual growth of the epiphysis and will eventually be converted totally to bone. 2. The results of an experiment which support this theory are described. A piece of developing joint cartilage was excised and replaced in its bed upside down. It was found that although the cartilage continued to proliferate at its normal rate, ossification of the original articular layer did not occur, so that there was a considerable increase in the thickness of the excised cartilage. 3. The supporting evidence for the hypothesis is discussed

Unlike hyaline cartilage, mandibular condylar cartilage can respond to injury by complete healing. We have used the reparative potential of mandibular cartilage to promote repair of defects in a hyaline cartilage joint surface. In 12 adult marmosets, articular fibrocartilage from the mandibular condyles was transplanted into full-thickness defects created in the femoral condyles. Additional defects acted as an ungrafted control group. The grafted defects showed good incorporation of the transplant with restoration of the articular surface within six months. Repair was by proliferation of the fibrocartilaginous graft and chondrogenesis of hyaline cartilage. The repopulating cells were distributed in a matrix of maturing collagen and sulphated glycosaminoglycans. Ungrafted control defects were only partly repaired with fibrous tissue, leaving articular deficiencies. We conclude that transplanted mandibular fibrocartilage can promote reconstitution of wounded hyaline cartilage joint surfaces in primates

The aim of this study was to evaluate the cultivation potential of cartilage taken from the debrided edge of a chronic lesion of the articular surface. A total of 14 patients underwent arthroscopy of the knee for a chronic lesion on the femoral condyles or trochlea. In addition to the routine cartilage biopsy, a second biopsy of cartilage was taken from the edge of the lesion. The cells isolated from both sources underwent parallel cultivation as monolayer and three-dimensional (3D) alginate culture. The cell yield, viability, capacity for proliferation, morphology and the expressions of typical cartilage genes (collagen I, COL1; collagen II, COL2; aggrecan, AGR; and versican, VER) were assessed. The cartilage differentiation indices (COL2/COL1, AGR/VER) were calculated. The control biopsies revealed a higher mean cell yield (1346 cells/mg vs 341 cells/mg), but similar cell proliferation, viability and morphology compared with the cells from the edge of the lesion. The cartilage differentiation indices were superior in control cells: COL2/COL1 (threefold in biopsies (non-significant)); sixfold in monolayer cultures (p = 0.012), and 7.5-fold in hydrogels (non-significant), AGR/VER (sevenfold in biopsies (p = 0.04), threefold (p = 0.003) in primary cultures and 3.5-fold in hydrogels (non-significant)). Our results suggest that the cultivation of chondrocytes solely from the edges of the lesion cannot be recommended for use in autologous chondrocyte implantation

Osteonecrosis of the femoral head can be caused by a variety of disorders and affects the relatively young patient. Most studies have concentrated on the femoral changes; the sites of early lesions of the labrum and acetabular cartilage have not been recorded. We studied 17 hips with osteonecrosis and a wide congruent joint space on radiographs and by direct inspection of the femoral head, labrum and acetabular cartilage during surgery. All of the femoral heads had some anterosuperior flattening which reduced the head-neck ratio in this area. A consistent pattern of damage to the labrum and the acetabular cartilage was seen in all hips. Intraoperatively, impingement and the cam-effect with its spatial correlation with lesions of the labrum and acetabular cartilage were observed. These findings could be helpful when undertaking conservative surgery for osteonecrosis, since the recognition of early radiologically undetectable acetabular lesions may require modification of the surgical technique

Four patients with injuries of the acetabular triradiate cartilage are presented. In three of them premature fusion of the cartilage occurred; two of these developed acetabular deformity and subluxation of the hip. In all patients the sacroiliac joint also was injured; in two, the joint was completely disrupted, leading to fusion and growth disturbance of the ilium. As injury of the triradiate cartilage is easily missed on the initial radiograph, it is advised that all patients with pelvic trauma should be followed clinically and radiographically for at least one year

The present investigation has shown that crude papain can be used to produce rapid changes in the epiphysial cartilage of various young laboratory animals (rabbits, mice, rats, guinea pigs and cats). 1. Single injections of crude papain produce profound changes in the epiphysial cartilage. These changes disappear within a few days. They are radiographically visible as a narrowing of the epiphysial plates. Histologically, the formation of bony trabeculae in the primary spongiosa is found to be arrested. 2. Repeated injections of crude papain cause permanent damage to the epiphysial cartilage, often with bony closure. Consequently, the longitudinal growth of the injected animals, when compared to the controls, is found to be retarded or permanently arrested, and there may be severe bony deformity. 3. Using inactivated crystalline papain, we have been able to produce changes in the epiphysial cartilage identical with those caused by the injection of crude papain. 4. The injection of crude papain is dispelled by the addition of cysteine, but retains its full strength if hydrogen peroxide is added