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PubMed2006

A preliminary in vitro study into the use of IL-1Ra gene therapy for the inhibition of intervertebral disc degeneration.

Conventional therapies for low back pain (LBP) are purely symptomatic and do not target the cause of LBP, which in approximately 40% of cases is caused by degeneration of the intervertebral disc (DIVD). Targeting therapies to inhibit the process of degeneration would be a potentially valuable treatment for LBP. There is increasing evidence for a role for IL-1 in DIVD. A natural inhibitor of IL-1 exists, IL-1Ra, which would be an ideal molecular target for inhibiting IL-1-mediated effects involved in DIVD and LBP. In this study, the feasibility of ex vivo gene transfer of IL-1Ra to the IVD was investigated. Monolayer and alginate cultures of normal and degenerate human intervertebral disc (IVD) cells were infected with an adenoviral vector carrying the IL-1Ra gene (Ad-IL-1Ra) and protein production measured using an enzyme-linked immunosorbent assay. The ability of these infected cells to inhibit the effects of IL-1 was also investigated. In addition, normal and degenerate IVD cells infected with Ad-IL-1Ra were injected into degenerate disc tissue explants and IL-1Ra production in these discs was assessed. This demonstrated that both nucleus pulposus and annulus fibrosus cells infected with Ad-IL-1Ra produced elevated levels of IL-1Ra for prolonged time periods, and these infected cells were resistant to IL-1. When the infected cells were injected into disc explants, IL-1Ra protein expression was increased which was maintained for 2 weeks of investigation. This in vitro study has shown that the use of ex vivo gene transfer to degenerate disc tissue is a feasible therapy for the inhibition of IL-1-mediated events during disc degeneration.

Adenoviridae↗

PubMed1995

Involvement of apoptosis in the induction of germ cell degeneration in adult rats after gonadotropin-releasing hormone antagonist treatment.

In adult mammals, including man, germ cell death is conspicuous during spermatogenesis and plays a pivotal role in sperm output. The possible mechanism(s) underlying this phenomenon remains, however, poorly understood. Apoptosis is a programmed physiological process by which cells die either spontaneously or in response to changes in the levels of specific physiological stimuli. Previously, we reported that early deprivation of gonadotropin and testosterone by GnRH antagonist (GnRH-A) treatment is followed by a stage-specific degeneration of germ cells in the testis. In this study, we examined the possible involvement of apoptosis in the induction of germ cell degeneration. Adult male rats were given a daily injection of Nal-Glu GnRH-A (1 mg/kg BW) for 0 (control), 2, or 5 days. The onset of germ cell degeneration was assessed by high resolution light microscopy as well as by a germ cell degeneration assay. The occurrence of apoptosis was characterized by 1) detection of internucleosomal DNA fragmentation after agarose gel electrophoresis, and 2) direct immunoperoxidase detection of digoxigenin-labeled genomic DNA in specific cell types. The earliest morphological signs of germ cell degeneration involving preleptotene and pachytene spermatocytes, step 7 spermatids (at stage VII), and step 19 spermatids (at both stages VII and VIII) were detected 5 days after the commencement of GnRH-A treatment. The onset of germ cell degeneration was further accompanied by a significant increase in the degree of low mol wt DNA fragmentation. In situ detection of apoptosis within this time frame fully corroborates the observed stage-related degeneration of specific germ cells. These results suggest that apoptosis provides the basic mechanism by which germ cells die in the testis in response to a lack of hormonal stimulation.

Animals↗

PubMed2004

Differences in the topographical distribution of articular cartilage degeneration between equine metacarpo- and metatarsophalangeal joints.

REASONS FOR PERFORMING STUDY: The equine metacarpophalangeal (MCP) and metatarsophalangeal (MTP) joints, although having virtually the same geometrical appearance, differ in the prevalence of joint pathologies, such as osteochondral fragmentation, and in biomechanical behaviour. The recently developed cartilage degeneration index (CDI) technique offers a possibility to assess quantitatively differences in cartilage degeneration between these joints and to compare these with known differences in biomechanics and clinical observations. OBJECTIVES: To compare the topographical distribution of articular cartilage degeneration across the proximal articular surface of the proximal phalanx (P1) in the equine fore- and hindlimb. METHODS: In 24 distal hindlimbs from 24 horses, articular cartilage degeneration of the proximal articular surface of P1 was quantified using the CDI. Overall CDI value (CDI(P1)) and CDI values of 6 areas of interest were determined: the medial dorsal surface (mds), lateral dorsal surface (lds), medial central fovea (mcf), lateral central fovea (lcf), medial plantar surface (mps) and lateral plantar surface (lps). The joints were divided into 4 equally sized groups of increasing CDI(P1) values. From an existing CDI database of MCP joints, 24 joints were selected with matching CDI(P1) values to the MTP joints and CDI values for the same areas of interest were determined. RESULTS: In both the MCP and MTP joints, highest CDI values were determined at the dorsal articular surfaces. Values were not significantly different between fore- and hindlimbs. In contrast to the MCP joint, CDI values at the plantar joint margin were significantly higher compared to CDI values in the central sites in the MTP joint. CDI values for the plantar surfaces of P1 were significantly higher than those for the palmar surfaces in the forelimb in joints with advanced stages of OA; and values for the central regions of P1 were significantly lower in the hindlimb compared with the forelimb in joints with severe OA. CONCLUSIONS: In both fore- and hindlimbs, initial cartilage degeneration started at the dorsal articular margin of P1. There was a major difference in the spread of cartilage degeneration; in the forelimb both the central and palmar parts are about equally involved, whereas in the hindlimb the plantar parts were significantly more and the central parts significantly less involved. These differences can be linked to differences in biomechanical loading reported elsewhere. POTENTIAL RELEVANCE: This study supports the hypothesis that differences in biokinematics between fore- and hindlimbs are associated with differences in the development of cartilage degeneration and other joint pathologies such as osteochondral fragmentation in the MCP and MTP joints. This information is indispensable for a better understanding of the dynamic nature and progression of these joint disorders and may be of help when monitoring the effects of therapeutic interventions and preventative measures.

Animals↗

PubMed1980

Hydrop degeneration. A histopathological investigation of 260 early abortions.

Placental tissue from 160 abortions provoked during the 6th--12th weeks, and 109 spontaneous abortions between weeks 5 and 16, were studied histopathologically on respect of a comparison and quantitation of hydrop degeneration. Significantly more cases of severe hydrop degeneration were observed among the spontaneous abortions (p < 0.001). Of these abortions, 87 per cent were hydrop degenerated to varying degrees; 41 per cent were severely hydrop degenerated. Among the provoked abortions, approximately 81 per cent were hydrop degenerated to varying degrees but only 6.9 per cent were severely hydrop degenerated. The relationship between severe hydrop degeneration and chromosome abnormality is discussed.

Abortion, Induced↗

PubMed1983

Degeneration of the gleno-humeral joint. An anatomical study.

One hundred and fifty-one shoulder dissections were performed on 76 cadavera, 41 men and 35 women, with an average age of 68 (range 18-92). Before the age of 60 no degenerative changes were encountered but after 60, degeneration and full thickness ruptures of the rotator cuff, cartilage degeneration and degeneration and ruptures of the long biceps tendon appeared in an increasing frequency with age. A highly significant relationship between cuff degeneration and cartilage degeneration was found. Measurement of the thickness of normal joint cartilage of the caput humeri did not show any changes with time. Gleno-humeral degeneration was encountered bilaterally in 82 per cent and was more frequent in women, and there is little evidence that occupation is of major importance for the development of shoulder joint degeneration.

Adolescent↗

PubMed1999

Relationship between morphology of iliolumbar ligament and lower lumbar disc degeneration.

Previous imaging studies have shown little difference in the degree of disc degeneration between L4-L5 and L5-S1. We hypothesized that because the morphology of the iliolumbar ligament affects the stability of the lumbosacral junction, then it could determine the lower lumbar disc degeneration. Fifty-three male and 47 female patients were classified into three groups according to their disc degeneration grade-those in whom the L5-S1 disc was less degenerated (group A), more degenerated (group B), and equally degenerated (group C) compared to the L4-L5 disc on T2-weighted magnetic resonance images. The length and direction of the anterior and posterior iliolumbar ligaments were measured on T1-weighted axial images. The iliolumbar ligament was shorter in group A than in group B or C, and was oriented significantly more posteriorly in group A than in groups B or C. The morphology of the iliolumbar ligament, especially its length and direction, can be a factor influencing the development of disc degeneration at L4-L5 and L5-S1.

Adult↗

PubMed1999

[Impact of fatty degeneration of the suparspinatus and infraspinatus msucles on the prognosis of surgical repair of the rotator cuff].

PURPOSE OF THE STUDY: Rupture of the cuff tendons can induce a fatty degeneration of cuff muscles. In 1989 the authors proposed a grading in 5 stages of this degeneration based on CT scan. The purpose of this study was to determine whether this degeneration had an influence on anatomical and clinical results after surgical repair of the cuff. MATERIAL AND METHODS: Seventy-four patients operated for a ruptured cuff had prospectively a pre-operative CT scan grading of muscular degeneration, and a post-operative anatomical control by opaque arthrography at about 10.5 months follow-up. Forty-four patients were males and 30 were females. The mean age at operation was 58.7 (40 to 75). Fifty-two ruptures were large involving the supraspinatus and infraspinatus in 17 cases, the supraspinatus and the subscapularis in 20 cases and all three tendons in 15 patients. Twenty-two ruptures were smaller and involved only the supraspinatus. To repair the cuff, it was necessary to advance the supraspinatus muscle in 28 cases and both supra and infraspinatus in 24 cases. No patient was lost for follow-up, and 51 of the 56 having more than one year of follow-up (mean 3 years, maximum 7.5 years) were evaluated according to Constant and Murley score. Two reoperated patients were excluded from the final analysis. RESULTS: Complete supraspinatus tears after repair recurred in 16 cases (22 p.cent). No infraspinatus rupture occurred after 32 infraspinatus repairs. Re-tears were observed only when a muscular advancement had been performed. Except in one case, re-tears occurred only when supraspinatus and/or infraspinatus were degenerated. The mean Constant score at revision for 49 patients was 66.6 points. According to this scoring system, 67.3 p.cent had a satisfactory result, 24.5 p.cent a fair result, and 8.2 p.cent a bad result. The mean score of the 39 patients having a continent cuff was 67.4 points, and was not significatively better than that of the patients with a re-tear (63.7 points). The best results were noted for the postero-superior tears (74.6 points). The type of repair had no significative influence on the final Constant score. The best improvements in external rotation were observed when a double advancement was performed. The stage of fatty degeneration, particularly of the infraspinatus, had an influence on the final range of motion, particularly in external rotation, and on the final strength. DISCUSSION: The fatty degeneration of supra and infraspinatus is an important prognostic factor of the anatomical and functional results after surgical repair of the cuff. More-over, when it is present, the surgeon may have some difficulties to close the tear during surgery. This study confirms that it is probably better to operate rotator cuff tears before the appearance of irreversible muscular damage, particularly when the lesions extend posteriorly to the supraspinatus.

Adipose Tissue↗

PubMed2001

The relationship between cartilage end-plate calcification and disc degeneration: an experimental study.

OBJECTIVE: To study the relationship between cartilage end-plate calcification and intervertebral disc degeneration. METHODS: An experimental model of cervical disc degeneration in rabbits was established by resection of the cervical supraspinous and interspinous ligaments and detachment of the posterior paravertebral muscles from the cervical vertebrae. Mechanical instability in the cervical spine elicited by this surgical intervention accelerated the process of intervertebral disc degeneration. The extent of intervertebral disc degeneration was graded in morphologically, and the thicknesses of the calcified layer and the uncalcified layer of the cartilage end-plate were measured in each degenerated cervical disc. RESULTS: In less severely degenerative cervical discs, the morphology of the cartilage end-plate showed nearly normal construction, and the tidemark was clear. In severely degenerative discs, the matrix and cells showed fibrosis, the tidemark advanced, and the calcified cartilage thickened. There exists a positive correlation between the thickness of the calcified layer of the cartilage end-plate and the degree of cervical disc degeneration. CONCLUSION: The calcification of the cartilage end-plate is the key factor that initiates and promotes cervical disc degeneration.

Animals↗

PubMed1999

[The relationship between cartilage end-plate calcification and disc degeneration: an experimental study].

OBJECTIVE: To study the relationship between cartilage end-plate calcification and intervertebral disc degeneration. METHODS: An experimental model of cervical disc degeneration in rabbits was established by resection of cervical supraspinous and interspinous ligaments and detachment of the posterior paravertebral muscles from cervical vertebrae. Mechanical instability in the cervical spine elicited by this surgical intervention accelerated the process of intervertebral disc degeneration. The degrees of intervertebral disc degeneration were graded morphologically. The thickness of the calcified layer and the uncalcified layer of the cartilage end-plate was measured in each degenerated cervical disc. RESULTS: A positive correlation existed between the thickness of the calcified layer of the cartilage end-plate and the degree of the cervical disc degeneration (r = 0.92). CONCLUSION: The calcification of the cartilage end-plate could initiate and promote intervertebral disc degeneration.

Animals↗

PubMed2003

Apoptosis and p53 expression in chondrocytes relate to degeneration in articular cartilage of immobilized knee joints.

OBJECTIVE: We have reported that articular cartilage showed early stage degeneration at 7 and 14 days after immobilization, moderate degeneration at 28 days, and severe degeneration at 42 days in rabbits. To test whether apoptosis occurs in association with p53 expression in chondrocytes during the process of articular cartilage degeneration, we investigated the degree of cartilage degeneration, the frequency of apoptotic cells, and the levels of p53 mRNA in rabbits and mice after knee immobilization. METHODS: Right knees of male Japanese white rabbits were immobilized in full extension with fiberglass casts for up to 42 days. Similarly, right knees of male p53 wild-type [p53 (+/+)] and p53 null [p53 (-/-)] mice were immobilized in full extension with bandage tape for up to 84 days. Apoptotic cells were confirmed by TUNEL staining on the sections of knee joints. Total RNA of articular chondrocytes obtained from Day 0 or immobilized knees was analyzed semiquantitatively by RT-PCR using specific primers for p53. RESULTS: Articular cartilage degenerated after immobilization of p53 (+/+) mouse knees, but not after immobilization of p53 (-/-) knees. Apoptotic cells were observed in articular cartilage in the femur and tibia of rabbits and p53 (+/+) mice after immobilization. However, only a few apoptotic cells were observed at the same sites in p53 (-/-) mice. In RT-PCR analysis, the levels of p53 mRNA obtained from immobilized groups were significantly higher than those of Day 0 groups in rabbit and p53 (+/+) mouse knees. CONCLUSION: Apoptosis and p53 expression in chondrocytes relate to degeneration in articular cartilage of immobilized knee joints.

Animals↗

PubMed2004

Gene expression profile of degenerated cervical intervertebral disc tissues in rats.

OBJECTIVE: To analyze the gene expression profile of degenerated cervical intervertebral disc of Sprague Dawley rats on a large scale. METHODS: Degenerated models of Sprague Dawley rats of 9 months old (degeneration group, n=9) and normal Sprague Dawley rats of 3 months old (control group, n=9) were prepared, respectively. mRNA was obtained from the cervical intervertebral disc of rats in both groups, respectively, and then labelled by Cy5 and Cy3 fluorescence respectively after reverse transcription to obtain intervertebral disc cDNA probes. cDNA probes were hybridized with BiostarR-40s gene expression profile chips and scanned by laser scanner. The results were treated with portrait analysis, standardization management, and ratio analysis with softwares. RESULTS: Compared with the rats in the control group, 9.6% (381 pieces in total) gene expression changed obviously in the rats in the degeneration group, among which, the gene expression quantities of 171 pieces increased significantly (r=the ratio of the degeneration group to the control group>2.0), 52 pieces of which had certain function. While the gene expression quantities of 211 pieces decreased significantly (r<0.5), 41 pieces of which had certain function. CONCLUSIONS: Gene chip technology can be used to analyze the gene expression profile of degenerated intervertebral disc of rats in parallel, in quantity and on a large scale, which helps to testify the representative genes and protein expression, and plays an important role in clarifying the pathogenesis of degenerated intervertebral disc.

Animals↗

PubMed2004

[The effect of disc degeneration on the structural property distributions in the cervical vertebral endplates].

OBJECTIVE: To study the effect of disc degeneration on the structural property distributions in the cervical vertebral endplates. METHODS: A 2 mm-diameter hemispherical indenter was used to perform indentation tests at 0.03 mm/s to the depth of 2 mm at 20 normalized locations in 50 bony endplates of intact human cervical vertebrae (C2 approximately C7). The resulting load-displacement curves were used to extract the failure load and stiffness of each test site. Grade of disc degeneration was determined using Nachemson's grading scale. One-way ANOVA, factorial analyses, SNK tests and correlate analyses were used to analyze the result data. RESULTS: Both the failure load and stiffness decreased with disc degeneration in the cervical endplates (P <0.001, both), and correlated significantly with the disc degeneration (rs=-0.429 and rs=-0.244, respectively). Only the distribution of superior cervical endplate changed with disc degeneration, but that of inferior cervical endplate changed little. CONCLUSIONS: The structural property distributions in the cervical vertebral endplates change significantly in the degenerated discs. It suggests that disc degeneration is an important factor to evaluate the intervertebral implant subsidence in anterior cervical fusion.

Biomechanical Phenomena↗

PubMed2004

[Frontotemporal dementia and frontotemporal degeneration--how to define?].

The term of the frontotemporal dementia was first proposed by Lund and Manchester group in 1994, but the definition of frontotemporal dementia has been still controversial. Frontotemporal dementia is caused by several diseases which have fronto-temporal atrophy. The diseases are collectedly designated as frontotempoal degeneration. The frontotemporal degeneration encompasses several diseases such as Pick disease (frontotemporal degeneration with Pick bodies) and frontotemporal degeneration with ubiquitin-positive inclusions and frontotemporal degeneration (no inclusion bodies are observed). Pick bodies are consisted of abnormally phosphorylated tau protein. The recent discoveries of tau mutations in frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) suggest important role of tau abnormalities in the disease mechanism. The frontotemporal degeneration has also another clinical phenotype such as slowly progressive aphasia. Slowly progressive aphasia has subtypes of non-fluent aphasia and semantic aphasia. Some patients with corticobasal degeneration or progressive supranuclear palsy also reveal the clinical pictures of frontotemporal dementia or slowly progressive aphasia and should be considered as differential diagnosis in the patients with frontotemporal dementia or slowy progressive aphasia.

Dementia↗

PubMed2005

[The effect of rupture and reconstruction of posterior cruciate ligament on the degeneration of articular cartilage in rabbit knee].

OBJECTIVE: To investigate the effect of rupture and reconstruction of the posterior cruciate ligament (PCL) on the degeneration of rabbit knee joint. METHODS: Thirty-three mature New Zealand white rabbits were divided into 3 groups. In experiment group I, the PCL of the right knees in 21 rabbits were resected, the contralateral joints as control group, in which only a medial arthrotomy was performed. In experiment group II, the PCL of the right knees in 12 rabbits were immediately reconstructed after PCL were resected. In experiment group I and control group the rabbits were respectively killed 6, 12 and 26 weeks after the operation. In experiment group II the rabbits were respectively killed 12, 26 weeks after the operation. The methods of ink staining, histology, immunohistochemistry and SEM were used to analyze the changes of articular cartilage of the joints. RESULTS: In experiment group I, the knee joints had obvious degeneration of articular cartilage at 26 weeks. The quantitative analysis of the results of the ink staining method showed the degeneration of knee articular cartilage was more serious at 26 weeks than that at 26 weeks in control group. Histological results demonstrated: the large area of fibrosis of cartilage could be seen in the medial condyle at 26 weeks; the fibrosis was deep into the deep layer of cartilage and the number of cells decreased; the average Mankin's score was 7.7. At 26 weeks, type I and III collagen were detected in fibrotic cartilage, while the staining of type II collagen was slight. In experiment group I, the injuries of cartilage in medial condyle could be seen at every stage through SEM, while the surface of cartilage demonstrated disorder in control group through SEM. In experiment group II, only a few specimens had mild injuries of cartilage, the degeneration of cartilage in medial condyle and trochlea were slighter at 26 weeks than that in experiment group I. CONCLUSIONS: PCL rupture can result in articular cartilage degeneration, which develops as time goes on. The degeneration of articular cartilage is more serious in medial compartment and patellofemoral joint than those in other positions. Immediate reconstruction of PCL can effectively prevent articular cartilage degeneration.

Animals↗

PubMed1994

Fatty muscle degeneration in cuff ruptures. Pre- and postoperative evaluation by CT scan.

A preoperative computed tomography (CT) scan grading muscular fatty degeneration in five stages was done in 63 patients scheduled for repair of a torn rotator cuff. The results were compared with postoperative evaluation done after a mean of 17.7 months in 57 patients. Postoperative arthrographies were also performed in 56 patients. Preoperative CT scans demonstrated that infraspinatus fatty degeneration can occur in the presence of large anterosuperior tears even when the infraspinatus tendon is not torn; it worsens with time. The subscapularis rarely degenerates, and when it does it degenerates moderately, even when its tendon is not torn. After an effective surgical repair, moderate supraspinatus degeneration regressed in six of 14 patients; that of the infraspinatus never regressed but rather, increased, in three patients. One of these deteriorations, involving both supra- and infraspinatus, could probably be attributed to a partial subscapular nerve injury. Infraspinatus degeneration was correlated with functional pre- and postoperative impairment of active external rotation. Recurrence of infraspinatus tear was never observed, but recurrence occurred in 25% of supraspinatus repairs. Infraspinatus degeneration had a highly negative influence on the outcome of supraspinatus repairs. It seems preferable to operate on wide tears before irreversible muscular damage takes place.

Adipose Tissue↗

PubMed1993

Degeneration of cervical intervertebral disks in fighter pilots frequently exposed to high +Gz forces.

This study investigated the occurrence and the degree of cervical disk degeneration among senior fighter pilots frequently exposed to high +Gz forces, compared with nonexposed controls matched for age and sex. A resistive magnetic resonance (MR) scanner operating at 0.1 T was used to image the cervical intervertebral disks. Sagittal MR images were obtained and disk degeneration was graded 0-6. Both the occurrence and the median degree of disk degeneration were greater among the pilots than among the controls. The greatest difference in the occurrence of disk degeneration (grades 1-6), which also reached statistical significance, was detected for the C3-4 disk: 88% among the fighter pilots and 64% among the controls, respectively. With respect to the moderate degenerative changes (grades 3 and 4) in the C3-4 disk, the difference in the occurrence (88% vs. 36%) was again statistically significant. There was no difference between the other disks. The median disk degeneration between the groups differed (2.0 vs. 1.0), the difference being the most remarkable (3.0 vs. 1.0) for the C3-4 disk. The differences in the median disk degeneration were also statistically significant. These findings suggest that frequent exposure to high +Gz forces may cause premature disk degeneration.

Adult↗

PubMed1995

Inflammatory leukocytic recruitment and diffuse neuronal degeneration are separate pathological processes resulting from traumatic brain injury.

The present study characterized whether inflammatory leukocytic infiltration is temporally and regionally correlated with neuronal degeneration and/or blood brain barrier (BBB) breakdown resulting from traumatic brain injury. Adult rats were sacrificed at 5 min, 2, 4, 12, 24, and 72 hr after lateral fluid percussion brain injury. BBB breakdown, neuronal degeneration and leukocyte infiltration were assessed using immunocytochemistry, silver impregnation and toluidine blue and eosin staining. BBB breakdown and neuronal degeneration occurred concomitantly in injured cortex, hippocampus, and along the dorsolateral quadrant of the diencephalon. However, neuronal degeneration within deep diencephalic structures transpired in the absence of IgG extravasation. Neutrophils were observed only in regions exhibiting BBB damage and were first apparent in injured cortex and hippocampus between 2-12 hr posttrauma lining the vasculature and filling subarachnoid/subdural spaces. Neutrophils then migrated from damaged vasculature into traumatized cortical and hippocampal parenchyma by 24 hr after lateral fluid percussion injury. Macrophages were also observed within cortical parenchyma at 24 hr and completely filled the cortical lesion site by 72 hr after injury. Macrophages were not as abundant throughout hippocampal parenchyma and were found only in hippocampal regions exhibiting focal hemorrhage at 72 hr. Finally, neutrophils did not migrate to deep diencephalic structures that showed no BBB damage despite extensive neuronal degeneration. Indeed, lateral fluid percussion elicits inflammatory leukocytic recruitment only in regions experiencing concomitant BBB damage and neuronal degeneration. In summary, inflammatory leukocytic recruitment and diffuse neuronal degeneration are separate pathological processes resulting from traumatic brain injury.

Animals↗

PubMed1997

Degenerated human articular cartilage at autopsy represents preclinical osteoarthritic cartilage: comparison with clinically defined osteoarthritic cartilage.

OBJECTIVE: To investigate whether macroscopically fibrillated human articular knee cartilage observed at autopsy can be considered an early, preclinical phase of osteoarthritis (OA). METHODS: Histological and biochemical characteristics of 3 types of articular knee cartilage were compared: macroscopically degenerated knee cartilage obtained at autopsy (6 donors) from donors without clinical history of OA, normal healthy knee cartilage obtained at autopsy (6 donors), and OA cartilage obtained during joint replacement surgery from patients (n = 6) with clinically defined OA of the knee. From the same donors synovial tissue and synovial fluid were obtained and analyzed for features of inflammation. RESULTS: Histological changes of OA were comparable for degenerated and OA cartilage and significantly different from normal cartilage. Content and synthesis of proteoglycans showed intermediate levels for degenerated tissue compared to normal and OA cartilage. Analysis of synovial tissue revealed a low, mild, and moderate degree of inflammation for joints with normal, degenerated, and OA cartilage, respectively. The same sequence was found for metalloproteinase activity in synovial fluid. CONCLUSION: In general, all changes observed in OA joints were, to a lesser extent, observed in the joints with degenerated cartilage and were significantly different from joints with normal cartilage. We conclude that cartilage degeneration observed at autopsy can be considered a preclinical phase of OA, suitable for studying the process of cartilage degeneration in OA.

Aged↗