Histopathological correlation of cartilage swelling detected by MRI in early experimental osteoarthritis

Department of Orthopaedic Surgery, Fundación Jiménez Díaz, Universidad Autónoma, Madrid, Spain.
Osteoarthritis and Cartilage (Impact Factor: 4.17). 12/2004; 12(11):878-86. DOI: 10.1016/j.joca.2004.07.007
Source: PubMed


We previously reported that an increase of cartilage thickness is the earliest measurable change by magnetic resonance imaging (MRI) in early stages of experimental osteoarthritis (OA). Our present objective was to study the microscopic translation of this finding in order to know whether the cartilage thickness increment represents the earliest structural damage or whether it alternatively constitutes a non-progressive reversible phenomenon.
OA was induced by partial medial meniscectomy in rabbits. Normal and sham-operated animals were used as controls. Gross and microscopic cartilage changes were sequentially assessed after surgery at 0, 2, 4, 6, 8, 10 and 52 weeks, and compared to MRI findings.
The swelling of cartilage detected by MRI correlated with depletion in matrix proteoglycans and cellular loss, which were closely related to the progression of OA at the earliest stages. Abnormalities of the cartilage structure appeared only in advanced OA.
Cartilage swelling detected by MRI is due to proteoglycan depletion and represents the earliest abnormality in OA. Because it is accompanied by cellular loss, it cannot be merely attributed to surgical trauma and represents true tissue damage. The biological meaning of volume variations detected by MRI should be assessed carefully taking into account the disease stage as an increase in cartilage height also reflects cartilage damage and not a reparative process.

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    • "In the present study, the development of OA was not still advanced at eleven weeks postsurgery, although it was enough to produce detectable changes in the articular cartilage but not in the subchondral bone. Articular cartilage appears in a state of swelling -characteristic of the early stages of the disease- previous to its erosion and destruction [35]. The subchondral bone, however, had not the typical sclerosis associated with this pathology, not appearing any differences between the healthy control group and the untreated OA group in any of the microstructural parameters analysed by either histology or micro-CT. "
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    ABSTRACT: The osteoarthritis (OA) treatment in humans and in animals is a major orthopaedic challenge because there is not an ideal drug for preserving the joint structure and function. The aim of this study was to assess the effects of the treatment with oral glucosamine and risedronate alone or in combination on articular cartilage, synovial membrane and subchondral bone in an experimental rabbit model of OA. Osteoarthritis was surgically induced on one knee of 32 New Zealand White rabbits using the contralateral as healthy controls. Three weeks later treatments were started and lasted 8 weeks. Animal were divided in four groups of oral treatment: the first group received only saline, the second 21.5 mg/kg/day of glucosamine sulfate, the third 0.07 mg/kg/day of risedronate; and the fourth group both drugs simultaneously at the same dosages. Following sacrifice femurs were removed and osteochondral cylinders and synovial membrane were obtained for its histological and micro-CT evaluation. Sample analysis revealed that the model induced osteoarthritic changes in operated knees. OA placebo group showed a significant increase in cartilage thickness respect to the control and inflammatory changes in synovial membrane; whereas subchondral bone structure and volumetric bone mineral density remained unchanged. All the treated animals showed an improvement of the cartilage swelling independent of the drug used. Treatment with glucosamine alone seemed to have no effect in the progression of cartilage pathology while risedronate treatment had better results in superficial fibrillation and in resolving the inflammatory changes of the tissues, as well as modifying the orientation of trabecular lattice. The combination of both compounds seemed to have additive effects showing better results than those treated with only one drug. The results of this animal study suggested that glucosamine sulfate and risedronate treatment alone or in combination may be able to stop cartilage swelling. The risedronate treatment could partially stop the fibrillation and the inflammation of synovial membrane as well as modify the orientation of trabeculae in healthy and in osteoarthritic knees.
    BMC Veterinary Research 04/2014; 10(1):97. DOI:10.1186/1746-6148-10-97 · 1.78 Impact Factor
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    • "The observers were blinded with respect to each other's reading, and rabbit group. Assessment of cartilage histology was performed at the weight-bearing surface of the medial femoral condyle because it shows the earliest and most severe histological abnormalities [37]. "
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    ABSTRACT: The receptor activator nuclear factor-kappaB ligand (RANKL) diffuses from articular cartilage to subchondral bone. However, the role of chondrocyte-synthesized RANKL in rheumatoid arthritis-associated juxta-articular bone loss has not yet been explored. This study aimed to determine whether RANKL produced by chondrocytes induces osteoclastogenesis and juxta-articular bone loss associated with chronic arthritis. Chronic antigen-induced arthritis (AIA) was induced in New Zealand (NZ) rabbits. Osteoarthritis (OA) and control groups were simultaneously studied. Dual X-ray absorptiometry of subchondral knee bone was performed before sacrifice. Histological analysis and protein expression of RANKL and osteoprotegerin (OPG) were evaluated in joint tissues. Co-cultures of human OA articular chondrocytes with peripheral blood mononuclear cells (PBMCs) from healthy donors were stimulated with macrophage-colony stimulating factor (M-CSF) and prostaglandin E2 (PGE2), then further stained with tartrate-resistant acid phosphatase. Subchondral bone loss was confirmed in AIA rabbits when compared with controls. The expression of RANKL, OPG and RANKL/OPG ratio in cartilage were increased in AIA compared to control animals, although this pattern was not seen in synovium. Furthermore, RANKL expression and RANKL/OPG ratio were inversely related to subchondral bone mineral density. RANKL expression was observed throughout all cartilage zones of rabbits and was specially increased in the calcified cartilage of AIA animals. Co-cultures demonstrated that PGE2-stimulated human chondrocytes, which produce RANKL, also induce osteoclasts differentiation from PBMCs. Chondrocyte-synthesized RANKL may contribute to the development of juxta-articular osteoporosis associated with chronic arthritis, by enhancing osteoclastogenesis. These results point out a new mechanism of bone loss in patients with rheumatoid arthritis.
    Arthritis research & therapy 06/2012; 14(3):R149. DOI:10.1186/ar3884 · 3.75 Impact Factor
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    • "It can be extremely useful to study the initial changes in OA. In human, MRI is replacing arthroscopy for evaluation of meniscal injuries as it enables noninvasive examination of the entire joint soft tissue as meniscus, including its tibial surface and the internal structure (Helms 2002; Martig et al. 2006), and also, it has been suggested to be used to evaluate the effect of therapies in cartilage tissue (Recht et al. 2001; Calvo et al. 2004). Several surgical procedures have been documented to cause experimental OA in the knee joint of animals following inducing instability (Fernando 1986; Pritzker 1994; Yoshioka et al. 1996; Bendele 2001) among which is the transection of cranial cruciate ligament (CCL) (Riitano et al. 2002; Papaioannou et al. 2007). "
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    ABSTRACT: The objective of the present study was to determine the magnetic resonance imaging (MRI) and gross pathological findings of articular cartilage in osteoarthritis experimentally induced in rabbit as an animal model. Ten adult Dutch male rabbits were randomly divided into two equal groups. In group one, in the left knee (stifle), the cranial (anterior) cruciate ligament (CCL) was sectioned [transected group (TG)], and in the second group, only arthrotomy was performed through the same approach, but the CCL was left intact [arthrotomy group (AG)]. In both groups, the right knees were considered as controls. Thirty days after operation, MRI was performed under general anesthesia, and then the animals were sacrificed for gross pathological study. MRI was performed by a 1.5-T scanner with a wrist coil to evaluate the coronal and sagittal gradient echo T2-weighted proton density and T1- and T2-weighted sequences. A magnification loupe was used to inspect the menisci, femoral and tibial cartilages, and synovium. The results revealed that the measured mean articular cartilage thickness by MRI was less in TG in comparison to AG and control groups (p < 0.05), whereas the difference between AG and control was not significant. Statistical analysis of the results revealed that the measured mean articular cartilage thickness by MRI was less in TG than those of AG and control groups, whereas the difference between AG and control was not significant. There were no significant differences in meniscal degeneration, joint effusion, and MRI overall grades between AG and the control groups. The difference was significant between TG with AG and the controls in relation to MRI findings. The gross examination revealed that there were no gross abnormalities in AG but there were also significant differences between the TG and AG, and between TG and the controls. Changes were localized primarily to the distal aspect of the medial femoral condylar cartilage. It was concluded that the MRI findings in early osteoarthritis process consisted of articular cartilage loss and meniscal degeneration. The quantitative alterations in articular cartilage thickness measured by MRI can be a noninvasive way to predict osteoarthritis. The MRI findings were also well correlated with the results of pathological study.
    Comparative Clinical Pathology 10/2009; 20(1). DOI:10.1007/s00580-009-0951-3 · 0.37 Impact Factor
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