Pathobiology of hemophilic synovitis I: overexpression of mdm2 oncogene

Hakobyan, Narine; Kazarian, Tamara; Jabbar, Adnan Abdul; Jabbar, Kausar J.; Valentino, Leonard A.

doi:10.1182/blood-2003-12-4231

Cited by 134 publications

(134 citation statements)

References 29 publications

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“…11 We postulated that the introduction of blood components, including endothelial cells capable of producing cytokines and angiogenic growth factors, may disrupt the homeostatic balance, thus favoring villous hypertrophy and increased vascularity. For personal use only.…”

Section: Discussionmentioning

confidence: 99%

“…11 Functionally validated primary ECs (BD Biosciences) were cultured with Clonetics EGM-2 endothelial growth medium (Cambrex). All experiments with ECs (second to fourth passages) and synovial cells (fourth to 15th passages) did not display discernable morphologic changes before each assay.…”

Section: Cell Culturementioning

confidence: 99%

“…Villous formation after a single hemarthrosis resulting from acid phosphatase and cathepsin D-induced synovial inflammation, 2 cartilage damage from long-lasting inhibition of proteoglycan synthesis, 9 and abrogated synovial apoptosis via iron-dependent increase in MDM2 expression and MYC-C amplification have been reported. [10][11][12] Neoangiogenesis is a critical factor in processes, such as tumor growth and inflammatory arthritis. 13 Vascular endothelial growth factor (VEGF), the principal signaling molecule in angiogenesis, can be induced by hypoxia and certain cytokines through interaction with its receptors, VEGFR1 and VEGFR2.…”

Section: Introductionmentioning

confidence: 99%

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Neoangiogenesis contributes to the development of hemophilic synovitis

Acharya

Kaplan

MacDonald

et al. 2011

Blood

110

121

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Joint arthropathy secondary to recurrent hemarthroses remains a debilitating complication of hemophilia despite the use of prophylactic factor concentrates. Increased vascularity and neoangiogenesis have been implicated in the progression of musculoskeletal disorders and tumor growth. We hypothesized that de novo blood vessel formation could play a major role in the pathogenesis of hemophilic joint disease (HJD). We observed a 4-fold elevation in proangiogenic factors (vascular endothelial growth factor-A [VEGF-A], stromal cell-derived factor-1, and matrix metalloprotease-9) and proangiogenic macrophage/monocyte cells (VEGF ؉ /CD68 ؉ and VEGFR1 ؉ /CD11b ؉ ) in the synovium and peripheral blood of HJD subjects along with significantly increased numbers of VEGFR2 ؉ /AC133 ؉ endothelial progenitor cells and CD34 ؉ / VEGFR1 ؉ hematopoietic progenitor cells. Sera from HJD subjects induced an angiogenic response in endothelial cells that was abrogated by blocking VEGF, whereas peripheral blood mononuclear cells from HJD subjects stimulated synovial cell proliferation, which was blocked by a human-

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Section: Discussionmentioning

confidence: 99%

Section: Cell Culturementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Neoangiogenesis contributes to the development of hemophilic synovitis

Acharya

Kaplan

MacDonald

et al. 2011

Blood

110

121

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“…In 90% of the patients aged 25 or younger a severe bleeding to major joint happens. [9][10][11][12][13][14] In our patient, recurrent bleeding into the knee joint caused secondary arthropathy. In patients with hereditary factor deficiency fresh frozen plasma (10-15 mL/kg) may be administered until hemophilia A or B diagnosis is reached.…”

Section: Case Reportmentioning

confidence: 61%

Previously undiagnosed hemophilia patient with intracerebral hemorrhage

et al. 2015

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“…The progressive accumulation of iron from red blood cells during successive intra-articular haemorrhages triggers synovial inflammation and may be a direct stimulus for the proliferation of synovial cells [15,16]. Free iron clearly promotes inflammation and cellular proliferation and is thought to play a role in the synovitis and excess angiogenesis observed in patients with haemophilia following repeated haemorrhage into a Ôtarget jointÕ [15][16][17]. Such a joint that has suffered repeated haemorrhage not only develops synovial proliferation but also florid angiogenesis that serves as a source of repeated bleeding.…”

Section: Discussionmentioning

confidence: 99%

Animal models of bleeding and tissue repair

Hoffman

2008

Haemophilia

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Summary. While a number of animal models have been developed for human haemophilia, it has been difficult to develop reproducible measures of bleeding in these models. They have also not been extensively utilized to study the complications of haemophilia beyond blood loss. Poor haemostatic function also leads to local haematomas, joint damage and poor wound healing. Some of the abnormalities related to bleeding are because of the deleterious effects of iron deposition in the tissues.Evidence from mouse skin wound and joint haemorrhage models suggests that bleeding and iron deposition initiate a vicious cycle of inflammation, angiogenesis and renewed bleeding. However, there is much yet to be learned about the effects of bleeding on tissue responses, including validating the results of animal studies in clinical trials.

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Pathobiology of hemophilic synovitis I: overexpression of mdm2 oncogene

Cited by 134 publications

References 29 publications

Neoangiogenesis contributes to the development of hemophilic synovitis

Neoangiogenesis contributes to the development of hemophilic synovitis

Previously undiagnosed hemophilia patient with intracerebral hemorrhage

Animal models of bleeding and tissue repair

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