The Reaction of Articular Cartilage to Injury and Osteoarthritis

Hj, Mankin

doi:10.1056/nejm197412122912406

Cited by 348 publications

(132 citation statements)

References 69 publications

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“…Acid and neutral proteases have been implicated as Possible causative agents in OA (12,18,19). Although pentosan polysulfate did not significantly alter tHe course of development of knee joint pathology in our studies, it is possible that the dose we selected is too high and that anionic polyelectrolytes of this type should be used in very low concentrations (Halse J: personal communication).…”

Section: Discussionmentioning

confidence: 80%

A new model of osteoarthritis in rabbits

Butler¹,

Colombo²,

Hickman³

et al. 1983

Arthritis & Rheumatism

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A battery of steroidal and nonsteroidal antirheumatic drugs and protease inhibitors were tested by intraarticular injection for effects on osteoarthritis of the knees of rabbits subjected to partial lateral meniscectomy and section of the sesamoid and collateral fibular ligaments. Among the standard drugs, only the glucocorticoid, triamcinolone hexacetonide, and the protease inhibitor, tranexamic acid, exhibited significant anti-osteoarthritic activity. An experimental drug, GPA 2163, also offered some protection against joint degeneration. The nonsteroidal antiinflammatory drugs had no effect on the development of osteoarthritis in the model.In a previous report from this laboratory, a new surgical method for experimental induction of osteoarthritis (OA) in rabbits was described (1). This method, which involves partial lateral meniscectomy and section of the sesamoid and collateral ligaments, induces a relatively consistent and reproducible degenerative disease of rabbit knees in a period of 6 weeks. A battery of selected steroidal drugs, nonsteroidal antiinflammatory drugs (NSAIDs), and other drugs reputed to possess antirheumatic properties or otherwise influence connective tissues have subsequently been tested for systemic efficacy in retarding or reversing the cartilage deterioration in knees of rabbits subjected to the new procedure (2). A few drugs exerted marked to moderate anti-OA activity. These included the steroids, paramethasone and triamcinolone, only 2 of 11 NSAlDs tested (pirprofen and the experimental drug, CGS 5391B), the glucofuranoside derivative, tribenoside, and the anti-estrogen, tamoxifen. The anti-osteoarthritic activity could not be explained in terms of known antiinflammatory or other properties of these drugs.In the present study, additional selected drugs have been tested for possible anti-OA efficacy by direct intraarticular (IA) injection in laterally meniscectomized rabbits. MATERIALS AND METHODSMale New Zealand white rabbits (Hare Farms) weighing approximately 4 kg each were subjected to partial lateral meniscectomy with section of the fibular collateral and sesamoid ligaments or sham operation, as previously described (1). The animals were maintained on a diet of standard rabbit pellets and tap water ad libitum.Intraarticular injections into the knee joint of test drugs or vehicle were given either as a single 0.0s ml dose 7 days post-surgery or as two 0.05 ml doses on days 7 and 14 post-surgery. The injections were made using 0.25-ml glass syringes and 26-gauge one-half-inch needles for soluble drugs or 23-gauge one-half-inch needles for suspensions. The source, dosage, and vehicle used for each test drug are shown in Table 1. One drug, triamcinolone hexacetonide, was also injected periarticularly (PA) in one group of rabbits (i.e., the compound was injected into the soft tissue immediately adjacent to the knee joint).In each rabbit tested, the right (operated) knee was injected with drug, while the left (unoperated) knee was injected with vehicle only, as a test for possible i...

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Section: Discussionmentioning

confidence: 80%

A new model of osteoarthritis in rabbits

Butler¹,

Colombo²,

Hickman³

et al. 1983

Arthritis & Rheumatism

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“…After 4 months of spontaneous healing the final repair tissue was histologically and grossly fibrocartilaginous, and attained neither morphologic nor molecular expression characteristics of normal articular cartilage. Such a mediocre response has functional consequences and it is well documented that intrinsic repair of fullthickness cartilage defects with fibrocartilage results in inferior biomechanical tissue properties, breakdown of the repair tissue, and frequently osteoarthritis [ 1, 19,27]. Longer term studies may have revealed better hyaline cartilage formation, however, the focus of this study was the characterization of early healing and the attendant changes in growth factor gene expression.…”

Section: Discussionmentioning

confidence: 99%

Insulin‐like growth factor‐I gene expression patterns during spontaneous repair of acute articular cartilage injury

Fortier

Balkman

Sandell

et al. 2001

Journal Orthopaedic Research

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This study evaluated the constitutive insulin-like growth factor-I (IGF-I) gene expression pattern in spontaneously healing cartilage defects over the course of 16 weeks, and correlated the tissue morphology and matrix gene expression with IGF-I mRNA levels. Full-thickness 15 mm cartilage defects were debrided in the femoral trochlea of both femoropatellar joints of 8 horses and the healing defects examined 2, 4, 8, or 16 weeks after surgery. Samples were harvested for histologic assessment of tissue healing using H&E staining, toluidine blue histochemical reaction for proteoglycan deposition, and in situ hybridization and immunohistochemistry procedures to demonstrate collagen type I1 mRNA and protein expression. Total R N A was isolated for Northern analysis to measure cartilage matrix molecule expression, and for semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) to determine IGF-I gene expression patterns in healing cartilage defects. Full-thickness cartilage defects in horses were slow to heal compared to smaller lesions in similar locations in other animals. However, a progressive decline in tissue cellularity and vascularity, and increased tissue organization were observed on H&E stained specimens over the 16-week experiment. Evidence of early chondrogenic repair was detected through collagen type 11 in situ hybridization and immunohistochemistry. However, levels of collagen type I1 and aggrecan mRNA in lesions were not abundant on Northern analysis indicating incomplete chondrogenesis. IGF-I message expression followed a cyclic pattern with low levels at 2 weeks, followed by an increase at 4 and 8 weeks, and a subsequent decline at 16 weeks. There was no direct correlation between the stage of healing and cartilage matrix message expression, and the abundance of IGF-I mRNA in the healing lesions. In conclusion, this study demonstrated that the spontaneous healing of articular defects was accompanied by a temporal fluctuation in IGF-I gene expression which was discoordinate to the steady rise in expression of cartilage matrix molecules such as procollagen type 11.

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“…Frontal sections (6 pm) were cut using a rotary microtome, and stained using safranin-O/fast green or haematoxylin and eosin. A modified Mankin grading system [26] was used to characterize the superficial surface structure, cellularity, safranin-0 staining characteristics, and tidemark integrity [21]. When examining the histology, the single observer was blinded as to the treatment.…”

Section: Hisroi?iotphonzettic Ussessment Of Cartilagementioning

confidence: 99%

Antiresorptive therapy conserves some periarticular bone and ligament mechanical properties after anterior cruciate ligament disruption in the rabbit knee

Doschak

Wohl

Hanley

et al. 2004

Journal Orthopaedic Research

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The purpose of this study was to assess, in an osteoarthritic (OA) model, whether bisphosphonate (BP) antiresorptive therapy altered periarticular bone and bone-ligament biomechanics and OA progression. We surgically transected the anterior cruciate ligament (ACLX) in two groups of rabbits; the first group was dosed with BP (risedronate, 0.01 mg/kg S.C. daily for 6 wk), the second group remained untreated, and a third group of normal (unoperated) control rabbits was also evaluated. We measured distal femoral bone mineral density (BMD, Dual Energy X-ray Absorptiometry [DEXA]), medial collateral ligament (MCL) laxity, and bone mechanical function (bone cores mechanically tested in compression). These measures were related to cartilage/joint gross morphology, histology, and measures of vascular volume (gelatin-dye perfusion) for evidence of inflammatory angiogenesis and early OA. BMD by DEXA in 6 wk ACLX animals was 18% less than normal controls (p < 0.05). In contrast, BP dosing conserved periarticular BMD; risedronate-treated rabbits had distal femoral BMD only 5% less and not significantly different than normal controls. When the same bone cores were compressed to failure, both ACLX and BPdosed animals were significantly weaker than normal controls (p < 0.05). However, the bone energy to failure and elastic modulus of BP-dosed animals was conserved and not significantly different from normal controls 6 wk after ACLX. Blocking bone resorption with BP also resulted in a significantly improved bone-ligament structural complex. MCL-complex laxity was significantly less in BP-dosed animals (1.2 times that of normal controls) compared to untreated ACLX animals (1.7 times that of normal controls; p < 0.05). Blocking bone resorption with risedronate did not suppress osteophytosis and inflammatory angiogenesis, which were significantly increased in the periarticular bone of both untreated and BP treated ACLX animals. Thus, administering BP immediately after ACL loss conserved some periarticular bone and MCL-complex properties in an early OA model.

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The Reaction of Articular Cartilage to Injury and Osteoarthritis

Cited by 348 publications

References 69 publications

A new model of osteoarthritis in rabbits

A new model of osteoarthritis in rabbits

Insulin‐like growth factor‐I gene expression patterns during spontaneous repair of acute articular cartilage injury

Antiresorptive therapy conserves some periarticular bone and ligament mechanical properties after anterior cruciate ligament disruption in the rabbit knee

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