Blood‐induced joint damage: A canine in vivo study

Roosendaal, G.; TeKoppele, J.M.; Vianen, M. E.; Berg, H. M. Van Den; Lafeber, Floris P. J. G.; Bijlsma, J. W. J.

doi:10.1002/1529-0131(199905)42:5<1033::aid-anr24>3.0.co;2-#

Cited by 119 publications

(109 citation statements)

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“…Throughout the years such changes are expected to lead to clinically diagnosable joint damage. 3,4 Unfortunately, little is known about the mechanisms that are responsible for these blood-induced adverse alterations in cartilage matrix turnover. Knowledge about these mechanisms is of importance in view of treatment of joint hemorrhages.…”

Section: Discussionmentioning

confidence: 99%

“…1,2 In vitro and animal in vivo studies provide evidence that not only repeated but also a relative short exposure of cartilage to blood results in long-lasting changes in chondrocyte metabolism that eventually may lead to cartilage destruction. 3,4 Such a short bleeding episode may be the first in a series in hemophiliacs but may also contribute to cartilage damage as the result of a sports injury or a single trauma, eg, ligament rupture. 5 After the initiation phase progression of joint damage in humans is slow.…”

mentioning

confidence: 99%

“…6,7 However, it became clear that, although these processes do contribute significantly to joint damage after repeated bleeding as in hemophilia, they are not the first to occur. [2][3][4] We showed that a short intra-articular bleeding episode in vivo or a short exposure of cartilage to blood in vitro induces lasting degenerative changes in cartilage independent of synovial inflammation and proinflammatory cytokine production. 4,8 Synthesis and release of matrix components such as proteoglycans are inhibited by blood in a concentration-dependent manner.…”

mentioning

confidence: 99%

“…[2][3][4] We showed that a short intra-articular bleeding episode in vivo or a short exposure of cartilage to blood in vitro induces lasting degenerative changes in cartilage independent of synovial inflammation and proinflammatory cytokine production. 4,8 Synthesis and release of matrix components such as proteoglycans are inhibited by blood in a concentration-dependent manner. It seems that these changes are the result of the combined presence of mononuclear cells (MNCs) and RBCs, whereas both cell types individually do not result in lasting changes.…”

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confidence: 99%

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Short-Term Exposure of Cartilage to Blood Results in Chondrocyte Apoptosis

Hooiveld

Roosendaal

Wenting

et al. 2003

The American Journal of Pathology

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Studies have shown that joint bleeding leads to cartilage degradation independent of concurrent synovitis. We hypothesized that the blood-induced cartilage damage is because of increased chondrocyte apoptosis after shortterm exposure of whole blood or isolated mononuclear cells plus red blood cells to cartilage. Human cartilage tissue samples were co-cultured for 4 days with whole blood (50% v/v) or with mononuclear cells plus red blood cells (50% v/v equivalents). Cartilage matrix proteoglycan synthesis ( 35 SO 4 2؊ incorporation) was determined after 4 days as well as at day 16 (after a 12-day recovery period in the absence of any additions). To test the involvement of apoptosis a specific caspase-3 inhibitor (acDEVDcho, 0 to 500 mol/L) as well as a pancaspase inhibitor (zVADfmk, 0 to 500 mol/L) were added. Chondrocyte apoptosis was evaluated by immunohistochemical staining of single-strand DNA and by terminal dUTP nick-end labeling. Cartilage co-cultured with whole blood as well as mononuclear cells plus red blood cells induced a long-term inhibition of proteoglycan synthesis (74% and 78% inhibition on day 16, respectively). Immunohistochemistry showed a threefold increase in apoptotic chondrocytes in cultures with 50% whole blood as well as with mononuclear cells plus red blood cells. Both the specific caspase-3 inhibitor and the pan-caspase inhibitor partially restored proteoglycan synthesis in the cartilage after blood exposure. This effect was accompanied by a decrease in the number of apoptotic chondrocytes. These data suggest that a single joint hemorrhage (a 4-day exposure of cartilage to 50% v/v blood) results in induction of chondrocyte apoptosis, responsible for the observed inability of the chondrocytes to restore the proteoglycan synthesis during recovery from a short-term exposure to blood. This reduced restoration could eventually lead to cartilage degeneration and ultimately joint destruction.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Short-Term Exposure of Cartilage to Blood Results in Chondrocyte Apoptosis

Hooiveld

Roosendaal

Wenting

et al. 2003

The American Journal of Pathology

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163

150

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“…Cartilage degradation was assessed by colorimetric assessment of glycosaminoglycan (GAG) release over 3 days into the culture medium of the cartilage samples, which were also assessed for retention of newly synthesized proteoglycans (see below) (45). GAGs were precipitated and stained with Alcian blue (Sigma).…”

Section: Methodsmentioning

confidence: 99%

Accumulation of advanced glycation end products as a molecular mechanism for aging as a risk factor in osteoarthritis

DeGroot¹,

Verzijl²,

Wijk

et al. 2004

Arthritis & Rheumatism

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Objective. Osteoarthritis (OA) is one of the most prevalent and disabling chronic conditions affecting the elderly. Its etiology is largely unknown, but age is the most prominent risk factor. The current study was designed to test whether accumulation of advanced glycation end products (AGEs), which are known to adversely affect cartilage turnover and mechanical properties, provides a molecular mechanism by which aging contributes to the development of OA.Methods. The hypothesis that elevated AGE levels predispose to the development of OA was tested in the canine anterior cruciate ligament transection (ACLT) model of experimental OA. Cartilage AGE levels were enhanced in young dogs by intraarticular injections of ribose. This mimics the accumulation of AGEs without the interference of other age-related changes. The severity of OA was then assessed 7 weeks after ACLT surgery in dogs with normal versus enhanced AGE levels.Results. Intraarticular injections of ribose enhanced cartilage AGE levels ϳ5-fold, which is similar to the normal increase that is observed in old dogs. ACLT surgery resulted in more-pronounced OA in dogs with enhanced AGE levels. This was observed as increased collagen damage and enhanced release of proteoglycans. The attempt to repair the matrix damage was impaired; proteoglycan synthesis and retention were decreased at enhanced AGE levels. Mankin grading of histology sections also revealed more-severe OA in animals with enhanced AGE levels.Conclusion. These findings demonstrate increased severity of OA at higher cartilage AGE levels and provide the first in vivo experimental evidence for a molecular mechanism by which aging may predispose to the development of OA.The population of Western society is aging rapidly. Consequently, age-related diseases will increase greatly over the coming decades and will have a great impact on the quality of life of the elderly. Osteoarthritis (OA) is one of the most prevalent and disabling chronic conditions affecting the elderly and poses a significant public health problem (1). The most prominent feature of OA is the progressive destruction of articular cartilage, resulting in impaired joint motion, severe pain, and, ultimately, disability (2). As yet, the etiology of OA remains largely unknown. The incidence of OA increases with age: Ͼ50% of the population over 60 years of age is affected (3,4). Although age is identified as the main risk factor for the development of OA, the mechanism by which aging is involved remains unclear. Age-related changes in the articular cartilage are expected to play an important role in the susceptibility of cartilage to OA.Articular cartilage derives its mechanical properties from its extracellular matrix. This matrix is composed of type II collagen, which forms a 3-dimensional network that provides the cartilage with resistance to tensile forces (5).

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