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Understanding the pathogenesis of equine osteoarthritis
Br. vet . /. (I99`?) . 148, :;till
GUEST EDITORIAL UNDERSTANDING THE PATHOGENESIS OF EQUINE OSTEOARTHRITIS
The study of May and his colleagues, reported in this issue of the Journal, uses timely in vitro methods to characterize the action of several stimuli oil the metabolic activity of equine chondrocytes and synoviocytes . It reveals that chondrocytes and synoviocytes respond to several chemical stimuli, including those which mimic traumatic and septic arthropathies, by releasing known mediators of cartilage breakdown . Osteoarthritis remains an important cause of lameness and impaired performance in athletic horses . Although many facets of the disease remain enigmatic, our understanding of the disorder is improving with advances in analytical techniques for the study of articular connective tissues . Osteoarthritis may now be regarded as a multifactorial syndrome with several potential initiating causes, all of which lead to degradative processes in the target organ, articular cartilage . Recent studies have shown that proteolytic enzymes are largely responsible for the degradation of matrix proteoglycans, the primary connective tissue component of articular cartilage. Continued loss of matrix proteoglycans ultimately results in the typical dirtical, radiographic, and pathological changes associated with osteoarthritis . The attention of many researchers in the field has been focused on the mechanisms of cartilage matrix loss and current thinking is that the chondrocyte itself may be the most important source of degradative enzyme activity in osteoarthritis . Although the synovial membrane is a source of these proteases, substantial inactivation of' these enzymes occurs by inhibitors in synovial fluid such as a 2-macroglobulin . Nonetheless, growing evidence suggests that the synovium contributcs significantly to the process of matrix depletion . The synovial lining is a source of several mediators known to activate chondrocvtic enzyme synthesis and release . Principal among these are certain cytokines, particularly interleukin-I and ttnnou r necrosis factor, generically known as cataholins . Interleukin-1 has heen isolated from the synovial fluid of arthritic equine : joints (M(rris Pt al., 1990 ; Alwaut ci al., 1991), and promotes several unfavourablee metabolic events including the release of matrix proteoglycans, synthesis of collagenase and other degradative en/\nucs, suppression of cartilage matrix synthesis, and inhibition of the response of chondrocvtes to various growth factors . Synoviocytes are a source of another likeh nrediator of matrix depletion, prostaglandin E" . This prostanoid has heen shown to induce proteoglycan loss from cartilage both in vitro and in vivo. Although no longer considered the primary means of matrix loss, tratuna is an important component of the pathogenesis of osteoarthritis . ( .vclical trauma to cartilage is known to enhance the concentration of the prostaglandin precursor ara-
3 70
RRt1ISI I Vi I t :RINAR\ JOURNAL . 11f 3
chidonic acid in chondrocyte membranes (Christnan el (it ., 1981) . Moreover . mechanical damage to an inherently sparse population of chondrocytes accelerates as matrix is lost . Characterization of the effects of cytokines, prostanoids, and other mediators is of interest to the clinician inasmuch as this information is virtually certain to lead to improved means of prevention and treatment of equine joint diseases . For example, certain non-steroidal anti-inflammatory drugs suppress cytokine synthesis by synovial cells (Herman et al., 1987) . Recent studies indicate that some anti-inflammatory preparations act by enhancing the synthesis of natural catabolin inhibitors (Herman et (il., 1989) . Despite recent advances, much is yet to be learned regarding the actions, interactions, and therapeutic control of the various mediators of osteoarthritis . For example, although commonly effective in blocking prostanoid synthesis and release, anti-inflammatory drugs may impair reparative responses (matrix synthesis) in cartilage (Palmosky et al., 1980) . Furthermore, proteoglycan loss may proceed in the presence of anti-prostaglandin medications, supporting the hypothesis that a host of mediators contribute to degradative processes . One potential group of mediators are peptides produced by articular nerves such as Substance P (Lotz et al ., 1987) . Osteoarthritis research using tissue culture techniques is a rapid and cost-effective method of obtaining information on joint metabolism in normal and diseased tissues and for the screening of new anti-arthritis drugs . Additional studies on the pathophysiological mechanisms of osteoarthritis, such as that described by May et al. in this issue, provide an excellent means of guiding clinical research and are integral to further our understanding of this complex and important disease . J . P . CARON
College of Veterinary Medicine, Michigan State University, East Lansing, Michigan 48824-1314, LISA
REFERENCES
AI .wAN,
W . H .,
CARTER,
S . D ., DixoN, J . B .,
BENNF:n,
D ., MAY, S . A. &
EDwARDS,
G. B . (1991) .
Interleukin-l-like activity in synovial fluids and sera of horses with arthritis . Res. vet . Sci . 51,72-7 . O . D .,
LADENRAUER-BELLIS, I . M ., PAN,IAeu, M . et al. (1981) . The relationship of mechanical trauma and the early biochemical reactions of osteoarthritic cartilage . Clin .
CHRISMAN,
Orthop . 161, 275-84 . J . H ., Ann,, A. M . & Hrss, E . V . (1987) . Modulation of cartilage destruction by select non-steroidal anti-inflammatory drugs . Arthritis Rheum 30, 257-65 . HERMAN, J . H ., Avi>Eu., A. M ., SOWDER, W . G ., BERGSTRAND, P. P. & HESS, E . V . (1989) . Piroxicam suppression of catabolin generation reflects induction of an interleukin-I (II : I) inhibitor (Abstr) . Arthritis Rheum 32, S50 . LOTZ, M., CARSON, D. A . & VAL'GHN, J . H . (1987) . Substance P activation of rheumatoid synoviocytes : neural pathway in the pathogenesis of arthritis . Science 235, 893-5 . HERMAN,
GLIEST EDITORIAL
37 1
MAY, S . A ., HooKE, R . E . & LEES, S. (1992) . Equine chondrocyte activation by a variety of
stimuli . Br. vet, j. 148, 389-97 . MORRIS, E . A., McDONAl,o, B . S ., WEBB, A. C . & RosSENW'ASSER, L . J . (1990) . Identification of interleukin-1 in equine osteoarthritic joint effusions . Am . j vel . Res. 51, 59-64 .
& BRANn'r, K. D. (1980) . Marked suppression by salicylate of the augmented proteoglycan synthesis (? matrix repair) in osteoarthritic cartilage .
PALMOSKY, M . J ., COYLER, R . A .
Arthritis Rheum 23,
83-91 .
GUEST EDITORIAL UNDERSTANDING THE PATHOGENESIS OF EQUINE OSTEOARTHRITIS
The study of May and his colleagues, reported in this issue of the Journal, uses timely in vitro methods to characterize the action of several stimuli oil the metabolic activity of equine chondrocytes and synoviocytes . It reveals that chondrocytes and synoviocytes respond to several chemical stimuli, including those which mimic traumatic and septic arthropathies, by releasing known mediators of cartilage breakdown . Osteoarthritis remains an important cause of lameness and impaired performance in athletic horses . Although many facets of the disease remain enigmatic, our understanding of the disorder is improving with advances in analytical techniques for the study of articular connective tissues . Osteoarthritis may now be regarded as a multifactorial syndrome with several potential initiating causes, all of which lead to degradative processes in the target organ, articular cartilage . Recent studies have shown that proteolytic enzymes are largely responsible for the degradation of matrix proteoglycans, the primary connective tissue component of articular cartilage. Continued loss of matrix proteoglycans ultimately results in the typical dirtical, radiographic, and pathological changes associated with osteoarthritis . The attention of many researchers in the field has been focused on the mechanisms of cartilage matrix loss and current thinking is that the chondrocyte itself may be the most important source of degradative enzyme activity in osteoarthritis . Although the synovial membrane is a source of these proteases, substantial inactivation of' these enzymes occurs by inhibitors in synovial fluid such as a 2-macroglobulin . Nonetheless, growing evidence suggests that the synovium contributcs significantly to the process of matrix depletion . The synovial lining is a source of several mediators known to activate chondrocvtic enzyme synthesis and release . Principal among these are certain cytokines, particularly interleukin-I and ttnnou r necrosis factor, generically known as cataholins . Interleukin-1 has heen isolated from the synovial fluid of arthritic equine : joints (M(rris Pt al., 1990 ; Alwaut ci al., 1991), and promotes several unfavourablee metabolic events including the release of matrix proteoglycans, synthesis of collagenase and other degradative en/\nucs, suppression of cartilage matrix synthesis, and inhibition of the response of chondrocvtes to various growth factors . Synoviocytes are a source of another likeh nrediator of matrix depletion, prostaglandin E" . This prostanoid has heen shown to induce proteoglycan loss from cartilage both in vitro and in vivo. Although no longer considered the primary means of matrix loss, tratuna is an important component of the pathogenesis of osteoarthritis . ( .vclical trauma to cartilage is known to enhance the concentration of the prostaglandin precursor ara-
3 70
RRt1ISI I Vi I t :RINAR\ JOURNAL . 11f 3
chidonic acid in chondrocyte membranes (Christnan el (it ., 1981) . Moreover . mechanical damage to an inherently sparse population of chondrocytes accelerates as matrix is lost . Characterization of the effects of cytokines, prostanoids, and other mediators is of interest to the clinician inasmuch as this information is virtually certain to lead to improved means of prevention and treatment of equine joint diseases . For example, certain non-steroidal anti-inflammatory drugs suppress cytokine synthesis by synovial cells (Herman et al., 1987) . Recent studies indicate that some anti-inflammatory preparations act by enhancing the synthesis of natural catabolin inhibitors (Herman et (il., 1989) . Despite recent advances, much is yet to be learned regarding the actions, interactions, and therapeutic control of the various mediators of osteoarthritis . For example, although commonly effective in blocking prostanoid synthesis and release, anti-inflammatory drugs may impair reparative responses (matrix synthesis) in cartilage (Palmosky et al., 1980) . Furthermore, proteoglycan loss may proceed in the presence of anti-prostaglandin medications, supporting the hypothesis that a host of mediators contribute to degradative processes . One potential group of mediators are peptides produced by articular nerves such as Substance P (Lotz et al ., 1987) . Osteoarthritis research using tissue culture techniques is a rapid and cost-effective method of obtaining information on joint metabolism in normal and diseased tissues and for the screening of new anti-arthritis drugs . Additional studies on the pathophysiological mechanisms of osteoarthritis, such as that described by May et al. in this issue, provide an excellent means of guiding clinical research and are integral to further our understanding of this complex and important disease . J . P . CARON
College of Veterinary Medicine, Michigan State University, East Lansing, Michigan 48824-1314, LISA
REFERENCES
AI .wAN,
W . H .,
CARTER,
S . D ., DixoN, J . B .,
BENNF:n,
D ., MAY, S . A. &
EDwARDS,
G. B . (1991) .
Interleukin-l-like activity in synovial fluids and sera of horses with arthritis . Res. vet . Sci . 51,72-7 . O . D .,
LADENRAUER-BELLIS, I . M ., PAN,IAeu, M . et al. (1981) . The relationship of mechanical trauma and the early biochemical reactions of osteoarthritic cartilage . Clin .
CHRISMAN,
Orthop . 161, 275-84 . J . H ., Ann,, A. M . & Hrss, E . V . (1987) . Modulation of cartilage destruction by select non-steroidal anti-inflammatory drugs . Arthritis Rheum 30, 257-65 . HERMAN, J . H ., Avi>Eu., A. M ., SOWDER, W . G ., BERGSTRAND, P. P. & HESS, E . V . (1989) . Piroxicam suppression of catabolin generation reflects induction of an interleukin-I (II : I) inhibitor (Abstr) . Arthritis Rheum 32, S50 . LOTZ, M., CARSON, D. A . & VAL'GHN, J . H . (1987) . Substance P activation of rheumatoid synoviocytes : neural pathway in the pathogenesis of arthritis . Science 235, 893-5 . HERMAN,
GLIEST EDITORIAL
37 1
MAY, S . A ., HooKE, R . E . & LEES, S. (1992) . Equine chondrocyte activation by a variety of
stimuli . Br. vet, j. 148, 389-97 . MORRIS, E . A., McDONAl,o, B . S ., WEBB, A. C . & RosSENW'ASSER, L . J . (1990) . Identification of interleukin-1 in equine osteoarthritic joint effusions . Am . j vel . Res. 51, 59-64 .
& BRANn'r, K. D. (1980) . Marked suppression by salicylate of the augmented proteoglycan synthesis (? matrix repair) in osteoarthritic cartilage .
PALMOSKY, M . J ., COYLER, R . A .
Arthritis Rheum 23,
83-91 .