Activation of extracellular matrix metalloproteinases in equine laminitis

Johnson, Philip J.; Tyagi, Suresh C.; Katwa, Laxmansa C.; Ganjam, Venkataseshu K.; Moore, L.A.; Kreeger, John M.; Messer, Nat T.

doi:10.1136/vr.142.15.392

Cited by 101 publications

(97 citation statements)

References 39 publications

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“…These phenomena might indicate that the keratinocytes comprising the regenerated LE has functional abnormality. Alternatively, activation of the reported MMPs relating with laminitis onset could dissolve the hemidesmosomes and anchoring fibrils in the BMZ even if it was promoting in the chronic stage [14]. However, latter explanation contradicts the evidence in which the intact lamina densa was seen in the BMZ through the TEM, because the reported MMPs can destroy not only type VII collagen or laminin 5 but also type IV collagen [14,27].…”

Section: Discussioncontrasting

confidence: 42%

“…Alternatively, activation of the reported MMPs relating with laminitis onset could dissolve the hemidesmosomes and anchoring fibrils in the BMZ even if it was promoting in the chronic stage [14]. However, latter explanation contradicts the evidence in which the intact lamina densa was seen in the BMZ through the TEM, because the reported MMPs can destroy not only type VII collagen or laminin 5 but also type IV collagen [14,27]. Further work is required for aspects of this immunohistochemical abnormality and the MMP activation.…”

Section: Discussionmentioning

confidence: 99%

“…In systemic acute laminitis disruption to the dermo-epidermal junction of the integument is known to be caused by the BMZ degradation [26]. This degradation results from the up-regulation of specific zinc-dependent endopeptidases such as matrix metalloproteinases 1, 2 and 9 (MMPs 1, 2 and 9) [14,22,27]. Its pathogenic process is similar to that of human epidermolysis bullosa [17,19,31].…”

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confidence: 99%

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Unilateral Basement Membrane Zone Alteration of the Regenerated Laminar Region in Equine Chronic Laminitis

et al. 2005

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ABSTRACT. Between the laminar epidermis and the laminar dermis of laminar region (LR) in equine foot, it can be observed the basement membrane zone (BMZ), which is composed of a basement membrane and its accompaniments like the hemidesmosome and anchoring fibril. Alteration in the BMZ in equine laminitis is possibly related with not only development but also recovery outcome and recurrence of this disease. However, there is little known about the structure of the BMZ during the recovery phase of this disease. To assess the condition of the BMZ of LR affected by chronic laminitis, the tissue was examined in three cases at two weeks, four weeks and three months after the onset of laminitis, using pathological, immunohistochemical and electron microscopic techniques. Histologically in all laminitis cases, there was a regenerated laminar epidermis with proliferating keratinocytes between the Stratum medium and the dermis, but it included the undeveloped secondary epidermal laminae (ud-SELs) structure in one side of the primary epidermal laminae, especially in the part of the deep area of LR. Immunohistochemical results were positive for the anti-type IV collagen, anti-type VII collagen and anti-laminin 5 antibodies in the most BMZs. However, partial BMZs adjacent to the ud-SELs were negative for the anti-type VII collagen and anti-laminin 5 antibodies. Ultrastructurally, in the BMZ of the ud-SEL, the lamina densa and the lamina lucida were present. In contrast, the anchoring fibrils and the hemidesmosomes were either absent, or present at lower than normal levels. In conclusion, the present study indicated that the part of regenerated LR in chronic laminitis was not able to fully restore to construct the BMZ for a long time, especially in the unilateral side of laminar epidermis. It might be related with recurrence of this disease. KEY WORDS: basement membrane zone, chronic laminitis, collagen, equine, laminin 5.J. Vet. Med. Sci. 67 (7): [685][686][687][688][689][690][691] 2005 The integumental tissues of the foot are important in supporting the horse's entire body weight during static and dynamic loading conditions. If severe intractable hoof disease occurs, the horse may lose not only the ability to run, but also to stand. Laminitis is one such intractable hoof condition and has a recurrent nature. Many horses have suffered from this disease over extended periods, resulting in significant treatment costs, and therefore the equine industry has a great deal of interest in clarifying the pathogenesis and developing treatment methods [5,9,12].Anatomically, the laminar region in foot displays a complex 3-dimensional structure consisting of the primary epidermal lamina (PEL) and the secondary epidermal lamina (SEL) which interdigitate with their dermal counterparts [24]. These dermal and epidermal components are separated by the basement membrane zone (BMZ), which is composed of a basement membrane and its accompaniments like the hemidesmosome and anchoring fibril [23]. The hemidesmosome, anchoring fibril and other c...

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Section: Discussioncontrasting

confidence: 42%

Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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Unilateral Basement Membrane Zone Alteration of the Regenerated Laminar Region in Equine Chronic Laminitis

et al. 2005

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“…4 was recognized in hooves from horses that had suffered laminitis for more than 10 days (case Nos. [5][6][7][8][9][10][11][12][13][14][15][16][17]. Moreover, in the hooves from horses that had suffered laminitis for more than 10 but less than 20 days (case Nos.…”

Section: Gross Observations Of Hoof Sectionsmentioning

confidence: 99%

A Gross and Histopathological Study of an Ectopic White Line Development in Equine Laminitis.

et al. 2002

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ABSTRACT. In horses with chronic laminitis, an abnormal horny structure called lamellar wedge, is generated between the hoof wall and the laminar epidermis. To be able to manage horses with chronic laminitis correctly, more information about the pathological state of this abnormal horn is required. The aim of this study was to collect and analyze objective morphological data about the abnormal horn in order to understand its morphology and development. In the study, the abnormal horn was grossly visible on the sagittal hoof section from approximately 20 days after the onset of disease. In the histological observations, the structural characteristics of this abnormal horn were similar to the white line tissue, suggesting it is an ectopic white line. Mean value of the cross-sectional area of the abnormal horn against the distal phalanx section area (A/D) was 0.29 cm 2 SD ± 0.14 and it finally showed an eight-fold increase over the mean value of normal white line section area against the distal phalanx section area. In conclusion, a large amount of the ectopic white line is thought to be finally able to inhibit normal hoof wall growth, so that it should be resected at the optimum time when would be after one month from the onset of the disease.

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“…[5][6][7][8][9] Locally released and activated MMPs mediate degradation of the collagen components of the basement membrane (BM) that is interposed between the secondary dermal (SDL) and epidermal lamellae (SEL) and cause a separation of the SEL from the BM. 4,[10][11][12][13][14] Sensory innervation of the foot consists of thick myelinated A-fibers (largely A β ) transmitting low-threshold mechanical information and small thin myelinated (A δ -fibers) and un-myelinated afferents (C-fibers) which express a variety of peptides and transmit high-threshold nociceptive information. [15][16][17][18][19] The A β fibers innervate lamellated corpuscles (comparable with Pacinian corpuscles) clustered below the digital cushion in the heel segment of the hoof that function as proprioceptors and provide a secure gait.…”

Section: Mechanisms Of Pain In Laminitismentioning

confidence: 99%