We have compared the concentrations of stromal-cell-derived factor-1 (SDF-1), matrix metalloproteinase-1 (MMP-1), MMP-9 and MMP-13 in serum before and after synovectomy or total knee replacement (TKR). We confirmed the presence of SDF-1 and its receptor CXCR4 in the synovium and articular cartilage by immunohistochemistry. We established chondrocytes by using mutant CXCR4 to block the release of MMPs. The level of SDF-1 was decreased 5.1- and 6.7-fold in the serum of patients with OA and RA respectively, after synovectomy compared with that before surgery. MMP-9 and MMP-13 were decreased in patients with OA and RA after synovectomy. We detected SDF-1 in the synovium and the bone marrow but not in cartilage. CXCR4 was detected in articular cartilage. SDF-1 increased the release of MMP-9 and MMP-13 from chondrocytes in a dose-dependent manner. The mutant CXCR4 blocked the release of MMP-9 and MMP-13 from chondrocytes by retrovirus vector. Synovectomy is effective in patients with OA or RA because SDF-1, which can regulate the release of MMP-9 and MMP-13 from articular chondrocytes for breakdown of cartilage, is removed by the operation

1. Chondromalacia, sometimes a precursor of osteoarthritis, is present in the articular cartilage of the patella of most people by the age of thirty; it causes symptoms in only a few, and it gives rise to osteoarthritis in fewer still. It may progress slowly or quickly but there is no clinical method of assessing the prognosis at an early stage. 2. The earliest change is swelling of the cartilage associated with a decrease in the chondroitin sulphuric acid content of the matrix. Later the cartilage fissures and flakes off to expose the bone, and there are reactive changes in the cartilage, bone and synovial membrane. The process is described and the etiology discussed. 3. The symptoms, signs and treatment are discussed. Operation, which has been performed only when there are disabling symptoms, may consist in removing part or the whole of the articular cartilage, or in excision of the patella. The results in forty-six knees are given

We studied the early cartilage changes in osteoarthritis, examining the most normal appearing articular cartilage from the hips of 17 patients. Normal appearing cartilage from five patients treated for fractures was used as control material. Two different types of clone were found. The first had increased staining for proteoglycan and was thought to have been engaged in the synthesis of matrix. The other type was associated with a severe deficiency of proteoglycan, matrix streaks and evidence of degradation and phagocytosis of matrix components. Immunohistochemistry demonstrated large amounts of chondroitin 4 and 6 sulphate about the synthetic-type clones, and little or no reactivity about the degenerative clones which lay more superficially and were associated with matrix destruction. Clones appeared to be engaged in either matrix synthesis or its destruction. The disease process of osteoarthritis appeared to begin at the surface of the articular cartilage

on in vitro incubation of articular and epiphysial cartilage of the ulna of the domestic pig 70 to 80 per cent of [U-. 14. C] glucose was metabolised to . 14. C-lactate, but cartilage of the epiphysial plate produced up to five times as much . 14. C-CO. 2. as articular cartilage, and the specific radioactivity of . 14. C (or . 35. S)-chondroitin 4 (6)-sulphate isolated from epiphysial cartilage (following . 35. S-sulphate incorporation) was about twice as high as that of articular cartilage. Six weeks after an osteotomy on both sides of the proximal epiphysial plate of the left ulna, the glucose uptake, lactate production, and the specific radioactivity of the glycosaminoglycans displayed no significant differences when compared with those of the corresponding epiphysial plate of the control right ulna, whereas a 50 per cent increase in the oxidation of . 14. C-glucose to . 14. c-co. 2. was observed

Aims

The use of 3D printing has become increasingly popular and has been widely used in orthopaedic surgery. There has been a trend towards an increasing number of publications in this field, but existing literature incorporates limited high-quality studies, and there is a lack of reports on outcomes. The aim of this study was to perform a scoping review with Level I evidence on the application and effectiveness of 3D printing.

Aims

The aim of our study is to investigate the effect induced by alternated mechanical loading on Notch-1 in mandibular condylar cartilage (MCC) of growing rabbits.

Primary osteoarthritis of the ankle with no history of trauma is rare. We report the use of a low tibial osteotomy on 18 ankles in 18 patients, two men and 16 women. The osteotomy is designed to correct the varus tilt and anterior opening of the distal tibial joint surface where it has been shown by weight-bearing radiographs and arthroscopy that there is healthy articular cartilage on the lateral side of the ankle. An opening-wedge osteotomy was used to achieve slight overcorrection. Follow-up of the 18 ankles at an average of 6 years 11 months (2.7 to 12.10) showed the results by our own scoring system to be excellent in six ankles, good in nine, and fair in three with no poor results. Of the three patients with fair results, two had been undercorrected and the third had little residual articular cartilage. Arthroscopic examination of ten ankles showed repair by fibrocartilage in seven. We conclude that slight overcorrection of deformity by low tibial osteotomy is effective in treating intermediate-stage primary osteoarthritis of the ankle

Biochemical changes in the articular cartilage of the knees of mature dogs, one with natural and four with surgically induced osteoarthritis, have been investigated. The four dogs were killed three, six, nine and forty-eight weeks after division of the right anterior cruciate ligament, the left knees serving as controls. The cartilage of the joints operated on was thicker and more hydrated than the control cartilage; the proteoglycans were more easily extracted and had higher galactosamine/glucosamine molar ratios. The proportion of proteoglycans firmly associated with collagen, and hence not extractable, diminished before fibrillation was demonstrable by indian ink staining of the surface. These biochemical changes were present throughout the entire cartilage of the joints operated on of the dogs killed more than three weeks later, and of the dog with natural osteoarthritis. The results suggest that in response to altered mechanical stresses the chondrocytes synthesise proteoglycans that contain more chondroitin sulphate relative to keratin sulphate than normally, as in immature articular cartilage

After a severe ankle sprain the incidence of residual complaints, particularly on the medial side of the joint, is high. We studied a consecutive series of 30 patients who had operative repair of acute ruptures of lateral ligaments. During operation, arthroscopy revealed a fresh injury to the articular cartilage in 20 ankles, in 19 at the tip and/or anterior distal part of the medial malleolus as well as on the opposite medial facet of the talus. In six patients, a loose piece of articular cartilage was found. We conclude that in patients with a rupture of one or more of the lateral ankle ligaments after an inversion injury, an impingement occurs between the medial malleolus and the medial facet of the talus. Patients with a lesion of the lateral ankle ligament caused by a high-velocity injury (a faulty landing during jumping or running) had a higher incidence of macroscopic cartilage damage (p < 0.01), medially-located pressure pain (p = 0.06) and medially-located complaints at one-year follow-up (p = 0.02) than those with a low-velocity injury (a stumble)

Damage to articular cartilage is a common injury, for which there is no effective treatment. Our aims were to investigate the temporal sequence of the repair of articular cartilage and to define a critical-size defect. Full-thickness defects were made in adult male New Zealand white rabbits. The diameter (1 to 4 mm) of the defects was varied in order to determine the effect that the size and depth of the defect had on its healing. The defects were made in the femoral groove of the knee with one defect per knee and eight knees per group. The tissues were fixed in formalin at days 3, 7, 14, 21, 28, 42, 84 and 126 after operation and the sections stained with Toluidine Blue. These were then examined and evaluated for several parameters including the degree of metachromasia and the amount of subchondral bone which had reformed in the defect. The defects had a characteristic pattern of healing which differed at different days and for different sizes of defect. Specifically, the defects of 1 mm first peaked in terms of metachromasia at day 21, those of 2 mm at day 28, followed by defects of 3 mm and 4 mm. The healing of the subchondral bone was slowest in defects of 1 mm

Autologous chondrocyte implantation (ACI) and mosaicplasty are both claimed to be successful for the repair of defects of the articular cartilage of the knee but there has been no comparative study of the two methods. A total of 100 patients with a mean age of 31.3 years (16 to 49) and with a symptomatic lesion of the articular cartilage in the knee which was suitable for cartilage repair was randomised to undergo either ACI or mosaicplasty; 58 patients had ACI and 42 mosaicplasty. Most lesions were post-traumatic and the mean size of the defect was 4.66 cm. 2. The mean duration of symptoms was 7.2 years and the mean number of previous operations, excluding arthroscopy, was 1.5. The mean follow-up was 19 months (12 to 26). Functional assessment using the modified Cincinatti and Stanmore scores and objective clinical assessment showed that 88% had excellent or good results after ACI compared with 69% after mosaicplasty. Arthroscopy at one year demonstrated excellent or good repairs in 82% after ACI and in 34% after mosaicplasty. All five patellar mosaicplasties failed. Our prospective, randomised, clinical trial has shown significant superiority of ACI over mosaicplasty for the repair of articular defects in the knee. The results for ACI are comparable with those in other studies, but those for mosaicplasty suggest that its continued use is of dubious value

Aims

Ageing-related incompetence becomes a major hurdle for the clinical translation of adult stem cells in the treatment of osteoarthritis (OA). This study aims to investigate the effect of stepwise preconditioning on cellular behaviours in human mesenchymal stem cells (hMSCs) from ageing patients, and to verify their therapeutic effect in an OA animal model.

The high prevalence of osteoarthritis (OA), as well as the current lack of disease-modifying drugs for OA, has provided a rationale for regenerative medicine as a possible treatment modality for OA treatment. In this editorial, the current status of regenerative medicine in OA including stem cells, exosomes, and genes is summarized along with the author’s perspectives. Despite a tremendous interest, so far there is very little evidence proving the efficacy of this modality for clinical application. As symptomatic relief is not sufficient to justify the high cost associated with regenerative medicine, definitive structural improvement that would last for years or decades and obviate or delay the need for joint arthroplasty is essential for regenerative medicine to retain a place among OA treatment methods.

Cite this article: Bone Joint Res 2021;10(2):134–136.

Aims

The diagnosis of joint infections is an inexact science using combinations of blood inflammatory markers and microscopy, culture, and sensitivity of synovial fluid (SF). There is potential for small molecule metabolites in infected SF to act as infection markers that could improve accuracy and speed of detection. The objective of this study was to use nuclear magnetic resonance (NMR) spectroscopy to identify small molecule differences between infected and noninfected human SF.

1. The methods by which epiphyses receive their blood supply was studied by means of India ink injections in monkeys. Two types were identified depending upon whether the epiphysis was entirely or partly covered by articular cartilage. In the former, nutrient vessels enter the epiphysis by traversing the perichondrium at the periphery of the plate. In the latter they enter the epiphysis by penetrating the cortex at the side of the epiphysis at a point remote from the epiphysial plate. 2. The histological changes after separation of the second type of epiphysis were also studied. After temporary interference with endochondral ossification marked by increased thickness of the epiphysial plate, healing occurred so rapidly that within three weeks it was difficult to determine that the epiphysis had been separated at all. 3. It is concluded that when nutrient vessels enter an epiphysis at a point remote from the epiphysial plate, that epiphysis can be separated without serious disturbance to its blood supply and accordingly without interference with its capacity for growth. As it has been established that an epiphysis which is entirely covered by articular cartilage cannot be separated without destruction of its blood supply and subsequent avascular necrosis (Harris and Hobson 1956), it is concluded that the prognosis of an epiphysial separation is dependent upon the degree of damage to its blood supply rather than the mechanical disturbance of the epiphysial plate

Osteoarthritis (OA), one of the most common motor system disorders, is a degenerative disease involving progressive joint destruction caused by a variety of factors. At present, OA has become the fourth most common cause of disability in the world. However, the pathogenesis of OA is complex and has not yet been clarified. Long non-coding RNA (lncRNA) refers to a group of RNAs more than 200 nucleotides in length with limited protein-coding potential, which have a wide range of biological functions including regulating transcriptional patterns and protein activity, as well as binding to form endogenous small interference RNAs (siRNAs) and natural microRNA (miRNA) molecular sponges. In recent years, a large number of lncRNAs have been found to be differentially expressed in a variety of pathological processes of OA, including extracellular matrix (ECM) degradation, synovial inflammation, chondrocyte apoptosis, and angiogenesis. Obviously, lncRNAs play important roles in regulating gene expression, maintaining the phenotype of cartilage and synovial cells, and the stability of the intra-articular environment. This article reviews the results of the latest research into the role of lncRNAs in a variety of pathological processes of OA, in order 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 2021;10(2):122–133.

Osteoarthritis, as seen in the hip, is a disease which eventually embraces all the tissues of the joint but begins as a reaction of the juxta-chondral blood vessels to a degeneration of the articular cartilage; this reaction results in a hyperaemia of the bone. To our surprise we found that daily use preserves rather than "wears out" articular cartilage; indeed inadequate use is the commonest cause of cartilage degeneration and ensuing vascular invasion. To this factor are added the effects of excessive pressure in the many patients who require surgical treatment for advanced osteoarthritis of a hip the seat of some anatomical incongruity. This etiology based on cartilage suffering does not exclude, but indeed explains, the osteoarthritis implanted on joints of a normal shape which have been previously affected by acute or chronic inflammation or by hormonal dysfunction, such as acromegalic osteoarthritis. The stimulus to vessel growth and invasion is the same in all these cases—namely cartilage damage. Once the vessels have entered the cartilage the bone and marrow of the osteophyte are inevitably laid down. What is so damaging in osteoarthritis seems to be not the degeneration of the cartilage but the vigorous and persistent attempt at repair, an attempt which aggravates the already disordered function of the joint not only by osteophyte formation but by the hypervascularity which weakens the structure of the bone beyond the point where it can carry its increased load. The collapse that follows provokes further reparative efforts with the same deplorable results. The osteoarthritic process thus appears to be an attempt to transform a decaying joint into a youthful one and for this, as in the miraculous rejuvenation depicted in Goethe's Faust, a high price must ultimately be paid