Effects of a bisphosphonate on bone histomorphometry and dynamics in the canine cruciate deficiency model of osteoarthritis.

OBJECTIVE: To examine the effect of the bisphosphonate NE- 10035 on bone histomorphometry and bone dynamics in dogs after transection of the anterior cruciate ligament (ACL), and to determine, in a placebo controlled trial, whether treatment modified the severity of pathologic changes of osteoarthritis (OA) in the unstable joint. METHODS: Ten adult male mongrel dogs underwent ipsilateral ACL transection. Five dogs then received daily subcutaneous injections of NE-10035 on 5 days per week for 12 weeks beginning the day after surgery. The other 5 dogs served as concurrent OA controls and received subcutaneous injections of saline on the same schedule. At sacrifice, 12 weeks after ACL transection, the articular cartilage and synovium of both knees of each dog were evaluated grossly and histologically and the water content and uronic acid concentration of the articular cartilage was determined. Fifteen days before sacrifice, each dog was injected with the fluorochrome label calcein. The injection regimen was repeated 10 days after the initial date. At sacrifice, static and dynamic variables of bone formation were assessed and bone resorption was quantified. RESULTS: In the OA knee of the control group, bone formation and resorption were markedly increased. NE-10035 markedly reduced both formation and resorption of cancellous subchondral bone, but had no effect on osteophyte formation or pathologic changes of OA in the articular cartilage, which were mild in both treatment groups. Water content of the OA cartilage was increased by about 8% in both treatment groups. However, among the controls, the mean uronic acid concentration of the OA cartilage was increased by about 30% in comparison with values for the contralateral knee, while in the NE-10035 treatment group the mean uronic acid concentration of OA knee cartilage was about 15% lower in the active treatment group than in cartilage from the contralateral knee (p = 0.003 for the difference in OA knee uronic acid concentration between the 2 treatment groups, relative to that in the contralateral knee). CONCLUSION: The antiresorptive agent employed in this study effectively reduced turnover of subchondral bone in the OA joint, consistent with the coupling of bone formation to bone resorption at that site. Nonetheless, over the 12 week period of the study it had no effect on osteophyte formation, in which bone formation occurs via enchondral ossification and is not linked to bone resorption, and, despite the clear inhibition of bone turnover in the OA knee of the active treatment group, did not affect the severity of cartilage changes of OA. It should be noted, however, that although treatment with this antiresorptive agent did not affect the level of chondropathy, the cartilage changes in both treatment groups were relatively mild and the sample size relatively small. Additional studies with a larger number of animals and a longer period of observation (to increase the severity of pathology) are warranted to determine whether the inhibition of bone turnover and the decrease in proteoglycan concentration that resulted from therapy will affect articular cartilage degeneration in the OA joint.

Sacroiliac joint innervation and pain.

The present paper reviews current knowledge on the innervation of the human sacroiliac joint (SIJ). We conclude, based on a recent anatomic study on adult cadavers, with fetal correlation, that the joint is predominantly, if not entirely, innervated by sacral dorsal rami. This conclusion is in agreement with patterns of referred pain reported by asymptomatic volunteers upon direct SIJ capsular stimulation and with a reduction in pain in patients treated for (presumptive) SIJ pain by injection of an anesthetic into the SIJ. We also present preliminary data suggesting that the periarticular tissues of the SIJ, like those of other synovial joints, contain mechanoreceptors and nociceptors that function to inform the central nervous system about the state of the joint.

Serial force plate analyses of dogs with unilateral knee instability, with or without interruption of the sensory input from the ipsilateral limb.

OBJECTIVE AND DESIGN: We characterized the mean peak vertical forces (MFz) in five groups of dogs which underwent transection of the left anterior cruciate ligament (ACLT) or sham ACLT and ipsilateral dorsal root ganglionectomy or sham-ganglionectomy, and the relationship of these forces to the severity of osteoarthritis (previously reported) 72 weeks after arthrotomy. Group I (N=7) underwent ACLT; Group II (N=8) underwent ACLT followed 52 weeks later by ganglionectomy; Group III (N=7) underwent ganglionectomy followed 2 weeks later by ACLT; Group IV (N=7) underwent sham-ganglionectomy followed 2 weeks later by ACLT; Group V (N=8) underwent ganglionectomy followed 2 weeks later by sham-ACLT. The dogs were evaluated 2, 6, 12, 24, 52 and 72 weeks after arthrotomy. RESULTS: From 6 weeks after arthrotomy until death, the left hindlimb MFz in Group V was significantly greater (P< 0.05) than that in the other four groups. The MFz of all groups which underwent ACLT decreased after arthrotomy. While the MFz of Group III (very severe OA) was about 10-20% greater than that of Groups I, II and IV (mild OA) 6 and 12 weeks after ACLT, and generally about 5-10% greater subsequently, this difference was not statistically significant. The MFz of Group II returned to pre-ganglionectomy levels, rather than to baseline levels, following ganglionectomy. CONCLUSIONS: (1) since the ipsilateral limb of dogs with ganglionectomy+sham ACLT bore normal amounts of weight throughout most of the postsurgical period, and its knee did not develop OA, one cannot argue that the knee was protected from OA because the limb was not used; (2) the fact that the MFz of dogs which underwent ACLT+ganglionectomy returned to pre-ganglionectomy levels, rather than baseline, is consistent with the hypothesis that the unstable joint was protected from accelerated breakdown by a central nervous system that was reprogrammed by sensation from the unstable limb; (3) the slightly-but consistently-greater MFz of dogs which underwent ganglionectomy+ ACLT may contribute to the acceleration of OA in this model.

Serial kinematic analysis of the canine hindlimb joints after deafferentation and anterior cruciate ligament transection.

OBJECTIVE AND DESIGN: Transection of the anterior cruciate ligament 2 weeks after ipsilateral hindlimb deafferentation leads to osteoarthritis of the knee joint within 3 weeks. We analyzed the gait of six dogs that underwent this procedure in order to identify kinematic changes that could account for this rapid joint degeneration. All animals were video taped, 1, 3, 6, 9 and 13 weeks after surgery while they trotted on a treadmill. RESULTS: In each dog, extension of the hip, knee and ankle joints of the unstable limb was increased, and the yield phase of the unstable knee was delayed or attenuated. When killed, five of six dogs showed a large full-thickness cartilage ulcer on the distal and/or anterior surface of the medial femoral condyle of the unstable knee; in the sixth dog, a smaller ulcer was observed. However, the severity of pathology in each individual was not obviously related to difference among the dogs in postoperative joint kinematics. CONCLUSIONS: These data, and results of prior studies in humans and dogs, suggest that knee hyperextension resulting from limb deafferentation, and knee instability resulting from anterior cruciate ligament transection, operate in concert to create a mechanical environment (i.e., increased tibiofemoral separation and changes in the loading of articular surfaces) that results in rapid joint breakdown.

Accelerated clearance of albumin from the osteoarthritic knee: implications for interpretation of concentrations of "cartilage markers" in synovial fluid.

OBJECTIVE: The magnitude of articular cartilage destruction or repair in osteoarthritic (OA) joints has been deduced in some studies from the synovial fluid (SF) concentration of proteins derived from the extracellular matrix of the cartilage, without regard to the low grade synovitis that is often present in this disease. We examined the clearance kinetics of albumin, as a surrogate for cartilage derived proteins, from OA and control joints in an established canine model. METHODS: Twelve weeks after the left anterior cruciate ligament of 6 normal dogs was transected, 131I albumin (RISA) was injected into the contralateral (control) knee. Surface radioactivity was monitored for 7 h, and SF was then aspirated to determine the SF RISA concentration and leukocyte count, and calculate the volume of distribution (VD) and clearance of RISA. One week later, RISA was injected into the cruciate deficient knee and these measurements were repeated, then the intensity of synovial inflammation and severity of cartilage changes of OA in both knees were assessed. RESULTS: Synovitis and articular cartilage ulceration were seen only in the cruciate-deficient OA knee, in which the mean SF leukocyte count (1570/mm3), thickness of the synovial intima (mean = 30 microns), and severity of synovial mononuclear cell infiltration (mean = 13,500 cells/mm2) significantly exceeded those in the contralateral knee (850/mm3, 13 microns, 1400 cells/mm2; p < or = 0.01 in each case). In each dog, RISA VD in the OA knee was higher than in the contralateral knee (mean = 9.2 +/- 3.6 and 3.7 +/- 0.9 ml, respectively; p = 0.008) and RISA clearance rate in the OA knee exceeded that in the contralateral knee (3.8 +/- 1.5 and 1.4 +/- 0.3 microliters/min, respectively; p = 0.009). CONCLUSION: Accelerated clearance of protein from the OA joint with low grade synovitis could significantly affect the SF concentration of cartilage derived proteins. Therefore, inferences about the effect of a therapeutic agent on cartilage metabolism based upon changes in the concentration of a protein in serial samples of OA SF may be misleading unless protein clearance kinetics have been determined.

Effects of oral doxycycline administration on histomorphometry and dynamics of subchondral bone in a canine model of osteoarthritis.

OBJECTIVE: To determine whether oral administration of doxycycline, in a dose that inhibits cartilage breakdown in a canine cruciate deficiency model of osteoarthritis (OA), affected formation or resorption of subchondral bone. METHODS: Ten healthy adult mongrel dogs underwent transection of the left anterior cruciate ligament. Five were given doxycycline, 3.5 mg/kg/day, orally, from the day after surgery until they were sacrificed 6 weeks later; the other 5 dogs served as positive OA controls. Three weeks before sacrifice, each dog was given an intravenous injection of the fluorochrome label, calcein, on each of 2 consecutive days; 10 days later, the injection regimen was repeated. At sacrifice, samples of bone from the medial femoral condyle of both knees of each dog were obtained for staining with Villanueva tetrachrome to localize the fluorochrome label and McNeal's tetrachrome for measurement of osteoid and cell counts. RESULTS: Cruciate deficiency resulted in a marked decrease in bone mass, with increased osteoclastic activity and increased bone formation. Doxycycline treatment did not significantly affect either bone formation or bone resorption. CONCLUSION: Doxycycline protects against joint breakdown in this OA model via inhibition of matrix metalloproteinases in articular cartilage, rather than through an effect on subchondral bone.

Serial kinematic analysis of canine hind limb joints after unilateral L4-S1 dorsal root ganglionectomy: Insights into locomotor control mechanisms.

Following unilateral L4-S1 dorsal root ganglionectomy to deafferent the hind limb, each of six dogs showed increased extension of the ipsilateral hip, knee and ankle joints during most of the gait cycle throughout a 26-week period of observation. The contralateral hind limb joints initially exhibited increased flexion during gait (which presumably compensated for the increased extension of the deafferented limb), but over time contralateral joint extension gradually increased, i.e. the movement of the joints of the contralateral limb progressively began to resemble that of the ipsilateral joints. We suggest that the long-term kinematic changes in both limbs (increased extension) occurred because of neurological changes in spinal cord structure, associated with death of sensory neurons and an associated increase in the influence of descending systems (e.g. vestibulospinal) on motoneurons. These results emphasize the importance of long-term observation of kinematic patterns after experimental induction of neural lesions and indicate that the contralateral limb should not, a priori, be considered a valid control in such studies.

Serial kinematic analysis of the canine knee after L4-S1 dorsal root ganglionectomy: implications for the cruciate deficiency model of osteoarthritis.

OBJECTIVE: To characterize knee movements before and after unilateral hindlimb deafferentation in dogs with stable joints. METHODS: High speed cinematography and frame by frame analysis were used to analyze knee kinematics of 6 dogs serially for 26 weeks following L4-S1 dorsal root ganglionectomy, which was performed to deafferentate one hindlimb. RESULTS: Overall knee movements were not reduced, but knee extension increased during most of the gait cycle. Few changes occurred in knee velocity, and none at touchdown or during weight acceptance. CONCLUSION: We previously showed that unilateral hindlimb deafferentiation does not cause osteoarthritis or reduce ipsilateral peak vertical forces in dogs with stable knee joints over an observational period of 16 months. We now show that joint protection in the deafferented stable joint occurs, paradoxically, in the presence of increased knee extension. We conclude that whereas sensory nerves may limit knee extension during ambulation, the health of the joint is not dependent upon this "extension limiting" function.

Serial kinematic analysis of the unstable knee after transection of the anterior cruciate ligament: temporal and angular changes in a canine model of osteoarthritis.

Transection of the anterior cruciate ligament in the dog leads to osteoarthritis. This study defines the kinematic changes in the unstable knee after transection of the cruciate ligament (six dogs) and after a sham operation (four dogs). In the dogs that were anterior cruciate ligament-deficient (ACL-D), the duration of stance 1 week postoperatively decreased 38% from the preoperative value, but only a 4% decrease was seen at 6 weeks. The duration of double hindlimb support increased from 6 to 19% of the entire cycle 1 week after surgery but returned to the baseline value by 18 weeks. As the unstable limb contacted the treadmill belt, the initial flexion (yield) and subsequent extension (propulsive) phases were not evident or were markedly attenuated in every ACL-D dog throughout the 26-week period of observation. The angular velocity patterns were characterized by a slight extension velocity at touchdown (compared with a zero value preoperatively) and a decrease in the peak velocities (both flexion and extension) during the remainder of the stance phase. None of these changes was observed in the animals that had a sham operation. These data indicate that, in the dog, the nervous system compensates for instability of the knee by altering angular, but not temporal, parameters. The extension velocity at touchdown and the reduction in peak flexion velocity during the yield component of the stance phase may reduce the ability of the limb to absorb impact forces and lead to the development of osteoarthritis of the knee.(ABSTRACT TRUNCATED AT 250 WORDS)

Serial kinematic analysis of the trunk and limb joints after anterior cruciate ligament transection: Temporal, spatial, and angular changes in a canine model of osteoarthritis.

To help elucidate how sensation-mediated kinematics modulate the rate of development of osteoarthritis in the unstable knee, we have examined the serial kinematic changes in hind- and forelimb joints, and alterations in vertical movement of the rump, in six dogs followed for 26 weeks after unilateral anterior curciate ligament transection. Although marked changes in the temporal parameters occurred in treadmill gait acutely in all four limbs, by the sixth postoperative week the stance and swing durations had returned to within ±10% of the baseline values, where they remained until sacrifice. As the cruciate-deficient limb contacted the treadmill surface, the amount of flexion (yield) of the unstable knee and ipsilateral ankle was reduced 10-20° (P < 0.05). In contrast, flexion of the contralateral ankle and knee increased about 10° during yield (P < 0.05), which was associated with a 100% increase in the extent of vertical movement of the rump (P < 0.05). Hip extension in the unstable limb increased about 10° during stance (P < 0.05), which moved the support provided by this limb away from the dog's centre of gravity. Kinematic changes in the forelimb joints were only transient, and less extensive than those in the hind limb. Before ligament transection, the joint angles of comparable joints of the different dogs were remarkably similar at touchdown. After ligament transection, the variability of the ipsilateral hip and knee joints was initially markedly increased. However, by 26 weeks after surgery the ipsilateral hip and knee touchdown joint angles of all the cruciate-deficient dogs were again similar to one another. Thus, after a period of 'trial and error', the dogs responded similarly to unilateral cruciate deficiency. This response was probably modulated by sensory nerves and reduced the trauma to the unstable knee during locomotion. Presumably, this facilitated effective, but suboptimal locomotion, while slowing the rate of progression of osteoarthritis in the unstable joint compared to dogs with a deafferented hind limb and unstable joint.

A longitudinal study of subchondral plate and trabecular bone in cruciate-deficient dogs with osteoarthritis followed up for 54 months.

OBJECTIVE: To evaluate the sequence of changes in articular cartilage, trabecular bone, and subchondral plate in dogs with osteoarthritis (OA), 3 months, 18 months, and 54 months after anterior cruciate ligament transection (ACLT). METHODS: Specimens of the medial tibial plateau were analyzed with microscopic computed tomography (micro-CT) at a resolution of 60 microns, and biochemical and morphologic changes in the femoral articular cartilage were assessed. RESULTS: At 3 months and 18 months after ACLT, the articular cartilage in the unstable knee showed histologic changes typical of early OA and increased water content and uronic acid concentration; by 54 months, full-thickness ulceration had developed. Micro-CT analysis showed a loss of trabecular bone in the unstable knee, compared with the contralateral knee, at all time points. At both 18 and 54 months, the differences in trabecular thickness and surface-to-volume ratio were greater than at 3 months. Although the mean subchondral plate thickness, especially in the medial aspect of the medial tibial plateau, was greater in the OA knee than in the contralateral knee 18 months and 54 months after ACLT, these differences were not statistically significant; however, the difference was significantly greater at 54 months than at 3 months. CONCLUSION: Thickening of the subchondral bone is not required for the development of cartilage changes of OA in this model. The bony changes that develop after ACLT, however, could result in abnormal transmission of stress to the overlying cartilage and thereby contribute to the progression of cartilage degeneration.

Sensory nerves only temporarily protect the unstable canine knee joint from osteoarthritis. Evidence that sensory nerves reprogram the central nervous system after cruciate ligament transection.

OBJECTIVE: The slow rate at which articular cartilage degrades in dogs after transection of the anterior cruciate ligament (ACLT) has been attributed to capsular thickening and buttressing by osteophytes. We investigated the roles of the peripheral and central nervous systems in protecting knee joints with chronic ACL deficiency from breakdown. METHODS: Five groups of dogs were studied; all were killed 72 weeks after left knee surgery. Group A had ACLT, group B had ACLT followed 52 weeks later by ipsilateral L4-S1 dorsal root ganglionectomy (DRG), group C had DRG followed 2 weeks later by ACLT, group D had sham DRG followed 2 weeks later by ACLT, and group E had DRG followed 2 weeks later by sham ACTL. RESULTS: Group E dogs did not develop knee pathology. All cruciate-deficient knees were lax at the end of the study. The osteoarthritis (OA) that developed in groups A, B, and D was comparable (P > 0.05), and was significantly greater than that in group E (P < 0.05). Group C developed much more severe OA than any of the other groups (P < 0.05). CONCLUSION: Ipsilateral sensory input is temporarily important in protecting the unstable joint from rapid breakdown. Over time, the central nervous system apparently acquires the ability to protect the unstable joint without continued ipsilateral sensory input.

Neurogenic factors in the etiopathogenesis of osteoarthritis.

In this article we have tried to unify several different lines of evidence bearing on how neuromuscular mechanisms might contribute to the etiopathogenesis of OA. Several key points bear emphasis. (1) The neuromuscular system is both the greatest threat that the joint faces and the principal means by which joints are protected, because this system exercises the definitive influence on the spectrum of forces to which the joint is exposed. If muscle contraction is not properly coordinated, the joint will exceed its normal extreme of excursion and the loading of its cartilage will be excessive. This trauma will be manifest pathologically as OA. It follows that if the neuromuscular system cannot control the mechanical environment of the joint, the articular and periarticular tissues will break down even in the face of treatment with "chondroprotective" drugs. (2) Speculation about the role of sensation in joint protection is pointless unless sensory ablation influences the development of OA. (3) Only a small minority of patients with severe peripheral sensory neuropathy develop a Charcot joint, and a clear correlation between the development of a Charcot joint and the severity of the sensory neuropathy or the activity level of the patient has yet to be established. Until proved otherwise, it should not be assumed that ipsilateral sensation plays a role in protecting the stable joint from breakdown. (4) There have been surprisingly few animal experiments in which the effect of sensory nerve ablation on synovial joints has been examined. Although the results of the early studies are not entirely consistent, they suggest that extensive deafferentation of a limb does not necessarily lead to joint pathology in the absence of exogenous trauma or infection. Such studies should be repeated under carefully controlled conditions. (5) Recent work in dogs suggests that ipsilateral sensation is not important in protecting the stable joint from OA but is necessary to protect the unstable joint from rapid deterioration. Moreover, there is evidence that sensation is temporarily important in protecting the unstable joint but that the CNS eventually acquires the ability to protect the unstable joint even in the absence of ipsilateral sensory input.

Reduction of the severity of canine osteoarthritis by prophylactic treatment with oral doxycycline.

OBJECTIVE: In vitro studies have indicated that levels of neutral metalloproteinases in osteoarthritic (OA) cartilage are elevated and that doxycycline (doxy) inhibits collagenolytic and gelatinolytic activity in extracts of OA cartilage. The purpose of the present study was to test the effect of oral doxy administration on the severity of cartilage degeneration in OA. METHODS: OA was induced in 12 adult mongrel dogs by transection of the anterior cruciate ligament (ACL) 2 weeks after dorsal root ganglionectomy. Six dogs received doxy orally from the day after ACL transection until they were killed 8 weeks later; the other 6 served as untreated OA controls. RESULTS: The unstable knee of each untreated dog exhibited extensive full-thickness cartilage ulceration of the medial femoral condyle. In sharp contrast, cartilage on the distal aspect of the femoral condyle of the unstable knee was grossly normal in 2 doxy-treated dogs, and exhibited only thinning and/or surface irregularity in the others. Degenerative cartilage lesions on the medial trochlear ridge, superficial fibrillation of the medial tibial plateau, and osteophytosis were, however, unaffected by doxy treatment. Collagenolytic activity and gelatinolytic activity in cartilage extracts from OA knees of untreated dogs were 5-fold and 4-fold greater, respectively, than in extracts from dogs given doxy. CONCLUSION: Prophylactic administration of doxy markedly reduced the severity of OA in weight-bearing regions of the medial femoral condyle. It remains to be determined whether administration of doxy after OA changes have developed is also effective.

Neurogenic acceleration of osteoarthrosis. The effects of previous neurectomy of the articular nerves on the development of osteoarthrosis after transection of the anterior cruciate ligament in dogs.

The development of osteoarthrosis in unstable knee joints of dogs after transection of the anterior cruciate ligament is greatly accelerated when the afferent nerve fibers from the ipsilateral hindlimb have been interrupted by dorsal root ganglionectomy before transection. The purpose of the current study was to determine whether partial loss of the afferent fibers from the knee joints of dogs, accomplished by neurectomy of the primary articular nerves before transection of the ligament, also accelerates the development of osteoarthrosis. Osteoarthrosis did not develop in dogs that had had transection of the medial, posterior, and lateral articular nerves to the left knee joint but had an intact anterior cruciate ligament. Osteoarthrosis developed in all dogs that had had transection of the anterior cruciate ligament. However, the osteoarthrotic lesions, as gauged by histological and macroscopic criteria, were more frequent and severe in dogs that had had neurectomy before transection than in those that had intact sensory nerves and an unstable joint (p less than or equal to 0.05). A subchondral fracture occurred in three dogs that had had neurectomy and had an unstable joint but in none of the dogs that had intact sensory nerves and an unstable joint.

Low dose prednisone treatment does not reduce the severity of osteoarthritis in dogs after anterior cruciate ligament transection.

It was reported recently that oral administration of prednisone, 0.3 mg/kg/day, decreased osteophyte size and cartilage ulceration in dogs with osteoarthritis (OA) produced by "stab" transection of the anterior cruciate ligament. Since this dose would be equivalent to 17 mg/day for a 70-kg human, our study was performed to determine whether a lower, clinically more realistic, dose of prednisone also had ameliorating effects on OA in the canine model. Following arthrotomy and transection of the anterior cruciate ligament 10 adult mongrel dogs were each given prednisone, 0.1 mg/kg/day, begun either 0, 2, or 4 weeks after arthrotomy and continued until sacrifice 12 weeks after surgery; 7 others underwent the identical surgical procedure but received no prednisone and served as OA controls. No differences were noted between dogs treated with prednisone and the controls with respect to size or extent of osteophytes, severity of synovial inflammation, morphologic changes of OA in articular cartilage, or in vitro synthesis of glycosaminoglycans. Increases in cartilage thickness in the OA knee were similar in the 2 groups, as were increases in H2O content and uronic acid concentration. Regardless of the interval between arthrotomy and start of treatment, the low dose of prednisone used here did not reduce the severity of OA in this model.

Synovitis and osteoarthritic changes in canine articular cartilage after anterior cruciate ligament transection. Effect of surgical hemostasis.

Anterior cruciate ligament transection (ACLT) in the dog produces changes in the articular cartilage of the unstable knee that are consistent with those of osteoarthritis (OA). To determine whether the degrees of severity of OA cartilage changes, of synovitis, and of synovial iron deposition were related to adequacy of hemostasis at the time of ACLT, a modified surgical technique was devised, whereby electrocautery was used to obtain meticulous control of bleeding when the ligament was severed and irrigation was used to remove intraarticular blood before closure of the joint. When no particular attention was given to hemostasis, 69% of the dogs showed synovitis in the OA knee 10 weeks after ACLT; when electrocautery and irrigation were used to maintain hemostasis, synovitis was present in only 24% of the OA knees 10 weeks after ACLT (P less than 0.01). Iron deposits were present in 75% of synovial samples obtained after routine ACLT, but in only 6% (P less than 0.001) when attention was given to hemostasis. Hypertrophy of articular cartilage, chondrocyte cloning, fibrillation, and changes in tangential zone chondrocytes were less prominent in the OA knee when electrocautery and irrigation were used. However, the water content, uronic acid concentration, and rate of net 35S-labeled glycosaminoglycan synthesis were similarly increased regardless of the surgical technique used, and presumably, these changes reflect the reaction of joint cartilage to mechanical instability in this model of OA.