Age-Related Histochemical and Histological Changes in the Knee-Joint Cartilage of C57B1 Mice and Their Significance for the Pathogenesis of Osteoarthrosis

Pataki, A.; Rüttner, J. R.; Abt, K.

doi:10.1159/000162998

Cited by 11 publications

(8 citation statements)

References 33 publications

(40 reference statements)

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“…Age-matched male mice of the normal CBA strain served as controls. The animals were killed by cervical dislocation, and their knee Accepted for publication 20 LDH media contained: 10 mg/ml sodium-DLlactate, 2 mg/ml NAD, 3 mg/ml neotetrazolium chloride, and 0-2 mg/ml phenazine methosulphate, at a final pH of 8 0. SDH media contained 10 mg/ml sodium succinate, 3 mg/ml BPST (a new tetrazolium salt),13 14 02 mg/ml phenazine methosulphate, at a final pH of 8 0.…”

Section: Methodsmentioning

confidence: 99%

A metabolic dysfunction in early murine osteoarthritis.

Altman¹

1981

Annals of the Rheumatic Diseases

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SUMMARY Male mice of the STR/ORT strain spontaneously develop an osteoarthritic lesion in the medial tibial condyle. The appearance of the lesion is age-related and by about 15 months has affected almost all animals. Histochemical studies of lactate dehydrogenase and succinate dehydrogenase activities have shown that a region of inactive chondrocytes appears in the cartilage of these mice before major histological evidence of degeneration. It is suggested that this may be an early metabolic dysfunction, which subsequently leads to matrix breakdown due to the lack of essential enzyme cofactors.Clues to the aetiology of osteoarthritis are most likely to be found in a study of the very early stages of the disease process.1 This is best achieved in an animal model, where the development of the lesion is well defined. Male mice of the inbred STR/ORT strain consistently develop an osteoarthritic lesion in the knee joint, specifically in the medial tibial condyle.2 3The lesion always occurs first close to the junction of the articular cartilage and the cruciate ligament, and subsequently spreads out across the whole condyle. The lateral condyles are not affected. There is an almost 100% incidence by the age of about 15 months. The lesion appears to be a result of an instability of the patella, which becomes displaced to the medial side; increased loads are thus transmitted through the medial condyle, and these are thought to initiate the degenerative changes.4Full details of the origins of these mice, from the parent STR/1N strain in the National Institutes of Health, Bethesda, Maryland, USA, have been given.2 They have also been extensively studied.3-7 In the present studies, they have been used in an attempt to define any metabolic changes which may occur in the chondrocytes before the histological appearance of degenerative changes in the articular cartilage. LDH media contained: 10 mg/ml sodium-DLlactate, 2 mg/ml NAD, 3 mg/ml neotetrazolium chloride, and 0-2 mg/ml phenazine methosulphate, at a final pH of 8 0. SDH media contained 10 mg/ml sodium succinate, 3 mg/ml BPST (a new tetrazolium salt),13 14 02 mg/ml phenazine methosulphate, at a final pH of 8 0. Both media were saturated with oxygen-free nitrogen before use. (SI conversion: g/l =mg/ml.) Materials and methods

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Section: Methodsmentioning

confidence: 99%

A metabolic dysfunction in early murine osteoarthritis.

Altman¹

1981

Annals of the Rheumatic Diseases

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“…Chondrocytes in mature cartilage, on the other hand, may lose the capacity to regulate UDPGD activity in this way, suggesting that agingrelated deregulation is the basis for the altered GAG synthesis profile that mature cartilage exhibits. This is supported by the loss of several other NAD-and NADP-linked dehydrogenase enzyme activities in OA-prone C57B1 mouse strains (54) and the fact that TGF-␤1 stimulates greater increases in PG synthesis in OA cartilage than in cartilage from normal human joints (55). Nevertheless, chondrocyte UDPGD activity in "nonweight bearing" regions of normal and OA human cartilage (mean age 75 and 64 years, respectively) do not appear to differ.…”

Section: Udpgd Activity/cell In Different Cartilage Zones Changes Assmentioning

confidence: 98%

Age-related Changes in the Response of Human Articular Cartilage to IL-1α and Transforming Growth Factor-β (TGF-β)

Hickery¹,

Bayliss

Dudhia

et al. 2003

Journal of Biological Chemistry

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Cartilage glycosaminoglycan (GAG) synthesis and composition, upon which its structural integrity depends, varies with age, is modified by anabolic and catabolic stimuli, and is regulated by UDP-glucuronate availability. However, how such stimuli, prototypically represented by transforming growth factor-␤1 (TGF-␤1) and IL-1␣, modify GAG synthesis during aging of normal human articular cartilage is not known. Using explants, we show that chondroitin sulfate (CS):total GAG ratios decrease, whereas C6S:C4S ratios increase with cartilage maturation, and that chondrocytes in the cartilage mid-zone, but not the superficial or deep zones, exhibit uridine 5-diphosphoglucose dehydrogenase (UDPGD) activity, which is also increased in mature cartilage. We also show that IL-1␣ treatment reduces both total GAG and CS synthesis, decreases C6S:C4S ratios (less C6S), but fails to modify chondrocyte UDPGD activity at all ages. On the other hand, TGF-␤1 increases total GAG synthesis in immature, but not mature, cartilage (stimulates CS but not non-CS), age-independently decreases C6S:C4S (more C4S), and increases chondrocyte UDPGD activity in a manner inversely correlated with age. Our findings show that TGF-␤1, but not IL-1␣, modifies matrix synthesis such that its composition more closely resembles "less mature" articular cartilage. These effects of TGF-␤1, which appear to be restricted to periods of skeletal immaturity, are closely associated although not necessarily mechanistically linked with increases in chondrocyte UD-PGD activity. The antianabolic effects of IL-1␣ are, on the other hand, likely to be independent of any direct modification in UDPGD activity and manifest equally in human cartilage of all ages.

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“…Spontaneous osteo-arthritis of the knee joint in mice has served for many years as an experimental model in studies of the aetiopathogenesis of the human disease [1][2][3][4][5] and in pharmacological investigations of potential antiarthrotic drugs [6,7]. Up to now, in pharmacological studies histopathological evaluation of mouse joints has been the only reliable means of assessing osteoarthritic changes.…”

Section: Introductionmentioning

confidence: 99%

Qualitative radiographic diagnosis of osteo-arthritis of the knee joint in the C57BL mouse

et al. 1987

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Experiments were performed to assess the diagnostic value of radiography in osteo-arthritis (OA) of the knee joint in C57Bl mice. Comparative histological and radiographic examination of knee joints from 96 animals showed that if the classical diagnostic criteria (narrowing of the joint space, sclerosis of the subchondral bone, deformation of the joint epiphyses) are applied, OA is not readily detectable by radiography. If these criteria are extended to include radiographic changes in the menisci (enlargement, deformation, increased and/or heterogeneous density), the frequency of detection is much improved. However, except in the severest forms of OA, radiography does not afford a satisfactory means of distinguishing between various degrees of severity. The qualitatively evaluated data nevertheless do suggest that quantitative radiographic diagnosis of OA of the murine knee joint may be useful, both for improving the detection rate and for discriminating various degrees of OA.

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Age-Related Histochemical and Histological Changes in the Knee-Joint Cartilage of C57B1 Mice and Their Significance for the Pathogenesis of Osteoarthrosis

Cited by 11 publications

References 33 publications

A metabolic dysfunction in early murine osteoarthritis.

A metabolic dysfunction in early murine osteoarthritis.

Age-related Changes in the Response of Human Articular Cartilage to IL-1α and Transforming Growth Factor-β (TGF-β)

Qualitative radiographic diagnosis of osteo-arthritis of the knee joint in the C57BL mouse

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