Mechanical determinants of osteoarthrosis.

https://www.oarsijournal.com/article/S1063-4584(03)00153-5/pdf

Pralnacasan, an inhibitor of interleukin-1β converting enzyme, reduces joint damage in two murine models of osteoarthritis

Osteoarthritis (OA) is a major cause of suffering for millions of people. Investigating the disease directly on humans may be challenging. The aim of the present study is to investigate the advantages and limitations of the animal models currently used in OA research. The animal models are divided into induced and spontaneous. Induced models are further subdivided into surgical and chemical models, according to the procedure used to induce OA. Surgical induction of OA is the most commonly used procedure, which alters the exerted strain on the joint and/or alter load bearing leading to instability of the joint and induction of OA. Chemical models are generated by intra-articular injection of modifying factors or by systemically administering noxious agents, such as quinolones. Spontaneous models include naturally occurring and genetic models. Naturally occurring OA is described in certain species, while genetic models are developed by gene manipulation. Overall, there is no single animal model that is ideal for studying degenerative OA. However, in the present review, an attempt is made to clarify the most appropriate use of each model.

Useful animal models for the research of osteoarthritis

Model systems are systems that are used to simplify complex phenomena and to understand otherwise elusive processes.' An animal model for human disease can be defined as a homogenous set of animals which have an inherited, naturally acquired, or experimentally induced biological process, amenable to scientific investigation, that in one or more respects resembles the disease in humans.2 3 Elusive and complex as a precise understanding may be, virtually all definitions of osteoarthritis express the disease as transient and progressive structural changes in joint tissues, principally articular cartilage, subchondral bone, synovium, and synovial fluid.4 Articular cartilage oedema, fibrillation, and erosion accompanied by chondrocyte proliferation and decreased staining of matrix proteoglycans, subchondral bone thickening, deformation of the articular surface, osteophyte formation, synovial intimal cell hyperplasia, and synovial fibrosis are some of the standard features associated with osteoarthritis. These changes result from a poorly understood but very large series of functional events which may occur over a large fraction of the life of each affected individual. Biochemical, cell or organ culture models can provide information and insight concerning the mechanisms for functional events within cartilage, bone or synovium or selected cells within these tissues. These ex vivo models, inherently more highly controlled than animal models, are most useful for understanding short term biological events, and events isolated from the physiological influences of adjacent structures and general metabolism. As yet, ex vivo models cannot simulate the structural changes which occur in joint tissues in animals over months to years. Hence, animal models for osteoarthritis are required to study how the complex structural changes in tissues evolve over time, spontaneously or following experimental injury, and to determine how constitutive, environmental or biomechanical risk factors4 may initiate, promote, or otherwise regulate these changes (table 1). Animal models are also needed to show how therapeutic strategies may ameliorate, resolve or prevent osteoarthritis.6 8 The decision to use a particular animal model to study osteoarthritis is governed by criteria of relevance, appropriateness, and availability.3 9 10 Relevance refers to the comparability of the phenomenon studied in animals to the corresponding process in human disease. Animals with characteristics similar to Table I Osteoarthritis: constitutional and eznvironmiiental factors

https://ard.bmj.com/content/annrheumdis/53/6/406.full.pdf

Animal models for osteoarthritis: processes, problems and prospects.

Male, 10-week-old C57B1 10 mice received a single intraarticular injection in the knee joints with papain, iodoacetate, or collagenase. This led to osteoarthritic lesions, such as matrix depletion, chondrocyte proliferation, and osteophyte formation, in the injected knee joints within several weeks. After injection of iodoacetate and papain, the main osteoarthritic alterations were localized in the femoropatellar joint, whereas injection of collagenase led to marked osteoarthritic lesions in the femorotibial joint. The mechanism of induction of these alterations appears to differ for iodoacetate and papain on one site and collagenase on the other site. Data are presented that collagenase injection, by way of damaging ligaments and tendons, destabilizes the knee joint eventually leading to osteoarthritic alterations. In contrast, injection of papain or iodoacetate directly interferes with cartilage metabolism resulting in osteoarthritic changes.

Development of osteoarthritic lesions in mice by "metabolic" and "mechanical" alterations in the knee joints.

The development of osteoarthrotic cartilage lesions in the knee joints of male STR/IN mice was studied with respect to their histologic appearance and their various localizations in the joint. Spontaneous articular cartilage degeneration on the medial portion of the tibial plateau was considered to be the initial event. Continued loss of cartilage subsequently led to a pronounced instability of the knee joint, with a varus deformity. This was followed by medial patellar luxation with corresponding osteoarthrotic lesions at the facies patellaris femoris. The most marked osteoarthrotic cartilage degeneration developed on the medial tibial condyle and at the facies patellaris femoris of the femoropatellar joint. Histologic examination of the osteoarthrotic defects in these two regions revealed distinct morphologic differences with respect to formation of chondrocyte clusters, tendency to regeneration, and proliferation reactions. Lectin binding experiments in normal articular cartilage revealed regional differences regarding the presence or absence of keratan sulfate in the extracellular matrix. The lack of keratan sulfate in tibial cartilage might reflect its tendency to degenerate spontaneously. It is therefore suggested that male STR/IN mice are particularly useful for studying two different types of osteoarthrosis, one due to a biomechanically induced instability (patellar luxation) and one due to biochemical changes (absence of keratan sulfate) of still unknown pathogenesis.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/art.1780310711

Morphologic characteristics of developing osteoarthrotic lesions in the knee cartilage of STR/IN mice.

Fluorescein-isothiocyanate (FITC) labeled lectins were used to study the distribution pattern of specific binding-sites in histological sections of normal and osteoarthrotic articular cartilage from the mouse knee joint. Male inbred mice of the STR/1N-strain develop spontaneous arthrotic articular cartilage lesions on the medial condyle of tibia and femur. The varus-deformity of the knee joint leads to a recurrent medial patellar luxation with osteoarthrotic defects on the medial part of the facies patellaris femoris. It was demonstrated that the lectin staining pattern of osteoarthrotic articular cartilage, especially on the facies patellaris femoris, was different from that of normal articular cartilage. The differences in lectin staining corresponded to those observed between normal and fibrillated articular cartilage from human patellae. The normal articular cartilage of the mouse knee joint possessed lectin binding-sites for Concanavalin A (ConA) and wheat germ agglutinin (WGA), but not for Ulex europaeus agglutinin (UEA), soy bean agglutinin (SBA) and peanut agglutinin (PNA). In addition to the completely changed distribution pattern of ConA and WGA in osteoarthrotic cartilage, SBA, PNA and UEA developed distinct staining patterns particular to the fibrillated areas of arthrotic cartilage. The increased lectin-binding to arthrotic articular cartilage may be due to unmasking of sugars in the course of bondage breakdown in fibrillated cartilage or the production of pathological glycoproteins. It is evident that lectins can demonstrate minute differences between normal and arthrotic cartilage and it is concluded, therefore, that lectins are sensitive and specific tools for the study of degenerative joint diseases.

Martina Brück

Papers

Morphologic characteristics of developing osteoarthrotic lesions in the knee cartilage of STR/IN mice.

Lectin-binding in normal and osteoarthrotic articular cartilage from STR/1N-mouse knee joints