Advances in the microscopy of osteoarthritis

Gardner, D. L.; Salter, Donald; Oates, K.

doi:10.1002/(sici)1097-0029(19970515)37:4<245::aid-jemt2>3.0.co;2-k

Cited by 27 publications

(12 citation statements)

References 156 publications

(106 reference statements)

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“…The first morphological alteration of the cartilage in the OA is the swelling of the superficial and middle zones of the extracellular matrix . This expands the cartilage matrix swelling, stretching the fibrous mesh of the surface region, resulting in the softening of the cartilage.…”

Section: Discussionmentioning

confidence: 99%

Diacerein reduces joint damage, pain behavior and inhibits transient receptor potential vanilloid 1, matrix metalloproteinase and glial cells in rat spinal cord

et al. 2015

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Section: Discussionmentioning

confidence: 99%

Diacerein reduces joint damage, pain behavior and inhibits transient receptor potential vanilloid 1, matrix metalloproteinase and glial cells in rat spinal cord

et al. 2015

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“…In early OA lesions within the joint surface, the chondrocytes distant from these lesions are capable of a coordinated response, leading to a distinct spatial reorganization introducing a novel spatial pattern (7). In contrast, chondrocytes within or adjacent to OA lesions undergo clustering that is typical of OA (8), in which unorganized aggregation results in the abandonment of typical spatial characteristics. During OA progression, chondrocytes may lose their sense of spatial order and their remodeling capability.…”

mentioning

confidence: 99%

Onset of preclinical osteoarthritis: The angular spatial organization permits early diagnosis

Rolauffs¹,

Rothdiener²,

Bahrs³

et al. 2011

Arthritis & Rheumatism

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Objective. Superficial articular chondrocytes display distinct spatial remodeling processes in response to the onset of distant osteoarthritis (OA). Such processes may be used to diagnose early events before manifest OA results in tissue destruction and clinical symptoms. Using a novel method of spatial quantification by calculating the angles between a chondrocyte and its surrounding neighbors, we compared maturational and degenerative changes of the cellular organizations in rat and human cartilage specimens.Methods. The nuclei of superficial chondrocytes obtained from intact rat cartilage and from human knee cartilage, as well as from cartilage with focal and severe OA, were digitally recorded in top-down views. Their Cartesian coordinates were used to determine the nearest neighbor for each chondrocyte and the angle between these 2 cells and a reference. These angles, cellularity, nearest neighbor distances, and aggregation were analyzed as a function of location and OA severity.Results. Neighboring rat chondrocytes exhibited intricate angular patterns with 4 dominant angles that were maintained during maturation and during the onset and progression of OA. Within intact cartilage, human chondrocytes demonstrated 1 dominant angle and, thus, a significantly different angular organization. With early OA onset, human chondrocytes that were located within intact cartilage displayed an increased occurrence of 4 angles; the resulting angular patterns were indistinguishable from those observed in rats. The angular remodeling was associated with location-and OA severity-dependent changes in cellularity and aggregation.Conclusion. This study is the first to identify the presence of angular characteristics of spatial chondrocyte organization and species-specific remodeling processes correlating with OA onset. The appearance of distinct angular and spatial patterns between neighboring chondrocytes can identify the onset of distant OA prior to microscopically visible tissue damage and possibly before clinical onset. With further development, this novel concept may become suitable for the diagnosis and followup of patients susceptible to OA.Articular cartilage is an autonomously functioning connective tissue, and its many properties depend on depth-dependent variations of its structure (1) and composition (2,3). Chondrocytes, although sparsely distributed throughout the extracellular matrix (ECM), maintain the intricate structure of articular cartilage (4). Over time, progressive cartilage damage frequently leads to degeneration and unavoidably to the development of clinical osteoarthritis (OA) (4). When OA is untreated, it causes severe disability and inflicts a considerable socioeconomic burden on the health care system. OA is characterized by the depletion of functionally relevant components of the ECM and consecutive degradation (5).

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“…A debate persists whether the disease process originates from the cartilage or the subchondral bone. However, it is commonly thought that OA develops in the majority of the patients at the level of chondrocytes62 and specifically at the articular surface63 64 where proliferative chondrocyte clones characteristically form at the margins of fibrillation 27 65. These chondrocyte clones are a histological hallmark of OA termed cell clusters.…”

Section: Reviewmentioning

confidence: 99%

“…Chondrocytes within or adjacent to OA lesions undergo an OA-typical clustering,65 in which unorganised aggregation results in the abandonment of typical spatial characteristics. We investigated whether such processes may be used to diagnose early OA events38 before manifest OA results in tissue destruction and clinical symptoms.…”

Section: Reviewmentioning

confidence: 99%

“…This response includes a spatial remodelling process whose underlying pathophysiology is not understood. Fibrillation-associated and lesion-associated cellular aggregation is related to chondrocyte proliferation 27 57 65 71 72. Proliferative factors such as basic fibroblast growth factor from the synovial fluid,73 cell shape changes, matrix depletion and disruption may induce proliferative cellular aggregation 45 74.…”

Section: Reviewmentioning

confidence: 99%

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The spatial organisation of joint surface chondrocytes: review of its potential roles in tissue functioning, disease and early, preclinical diagnosis of osteoarthritis

Aicher

Rolauffs²

2013

Ann Rheum Dis

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Chondrocytes display within the articular cartilage depth-dependent variations of their many properties that are comparable to the depth-dependent changes of the properties of the surrounding extracellular matrix. However, not much is known about the spatial organisation of the chondrocytes throughout the tissue. Recent studies revealed that human chondrocytes display distinct spatial patterns of organisation within the articular surface, and each joint surface is dominated in a typical way by one of four basic spatial patterns. The resulting complex spatial organisations correlate with the specific diarthrodial joint type, suggesting an association of the chondrocyte organisation within the joint surface with the occurring biomechanical forces. In response to focal osteoarthritis (OA), the superficial chondrocytes experience a destruction of their spatial organisation within the OA lesion, but they also undergo a defined remodelling process distant from the OA lesion in the remaining, intact cartilage surface. One of the biological insights that can be derived from this spatial remodelling process is that the chondrocytes are able to respond in a generalised and coordinated fashion to distant focal OA. The spatial characteristics of this process are tremendously different from the cellular aggregations typical for OA lesions, suggesting differences in the underlying mechanisms. Here we summarise the available information on the spatial organisation of chondrocytes and its potential roles in cartilage functioning. The spatial organisation could be used to diagnose early OA onset before manifest OA results in tissue destruction and clinical symptoms. With further development, this concept may become clinically suitable for the diagnosis of preclinical OA.

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Advances in the microscopy of osteoarthritis

Cited by 27 publications

References 156 publications

Diacerein reduces joint damage, pain behavior and inhibits transient receptor potential vanilloid 1, matrix metalloproteinase and glial cells in rat spinal cord

Diacerein reduces joint damage, pain behavior and inhibits transient receptor potential vanilloid 1, matrix metalloproteinase and glial cells in rat spinal cord

Onset of preclinical osteoarthritis: The angular spatial organization permits early diagnosis

The spatial organisation of joint surface chondrocytes: review of its potential roles in tissue functioning, disease and early, preclinical diagnosis of osteoarthritis

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