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Title: Age, Segment, and Horn Disease Affect Expression of Cytokines, Growth Factors and Receptors in the Epidermis and Dermis of the Bovine Claw

item MILLS, J - Thomas Jefferson University
item Zarlenga, Dante
item HABECKER, P - University Of Pennsylvania
item DYER, R - University Of Delaware

Submitted to: Journal of Dairy Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/11/2009
Publication Date: 12/1/2009
Citation: Mills, J.A., Zarlenga, D.S., Habecker, P.L., Dyer, R.M. 2009. Age, segment, and horn disease affect expression of cytokines, growth factors and receptors in the epidermis and dermis of the bovine claw. Journal of Dairy Science. 92:5977-5987.

Interpretive Summary: Dairy cattle lameness arises primarily from disorders of the hind limb, lateral claw capsule. Epidemiologic evidence established dietary and housing factors interact to cause claw horn lesions but the pathophysiology underlying these associations has been poorly investigated. The purpose of this investigation was to address four questions related to immune responses, growth factors and receptors present in the claw: (1) Do epidermal-dermal horn producing tissues of the bovine claw express immune related molecules known to orchestrate tissue homeostasis in the integument? (2) Are expression levels congruent among the different regions of the claw? (3) Are expression levels within and between different regions of the claw related to host, and; (4) Does the disease state of the claw horn affect expression levels throughout the claw. Our results showed that growth factor and cytokines regulating tissue growth and differentiation in the integument were expressed in horn producing tissues of the claw. Inflammation, bleeding and horn damage disturbed expression of immune related genes and growth factors throughout the claw. The success in answering the above questions generated important information on early detection signs of lameness and established a model to study methods of treating this debilitating disease among dairy cows.

Technical Abstract: The aim of this study was to examine changes in amounts of RNA expression for growth factors, cytokines and receptors in epidermal-dermal tissues of the bovine claw relative to host age, claw region and disease state of the horn. Epidermal-dermal tissues were collected from the coronette, wall, sole, and bulb regions of 8-9 month Holstein fetuses, normal adult cows and adult cows with sole ulceration. Anatomic and pathologic characteristics were determined in tissues stained with eosin and hematoxylin and RNA expression levels were evaluated using real time quantitative polymerase chain reaction. In normal tissues, certain RNA expression levels were clearly affected by host age in which 290.0, 610.0, 53.4 and 8.1 fold greater expression of granulocyte-macrophage colony stimulating factor was observed in fetal coronette, wall, sole, and bulb, relative to adult tissues. Regional effects were also observed in which interleukin-1 alpha expression was greater (1.59x) in the normal adult wall relative to the coronette, and interleukin 18 expression was greater (16.2x) in the normal adult sole compared with the coronette, and 2.88 greater in the fetal sole relative to the bulb. Claw horn disease was associated with hemorrhage, thrombosis and inflammation, striking increases in interleukin-1 beta, interleukin 18, inducible nitric oxide synthase and less dramatic albeit measurable changes in interleukin 1 type I receptor, the interleukin 1 receptor antagonist and tumor necrosis factor – alpha. Amidst striking increases in keratinocyte growth factor receptor i.e.21.0, 10.4, 0 and 21.6 in the coronette, wall, sole, and bulb respectively, a concomitant decrease occurred in keratinocyte growth factor i.e. 5.0, 2.2, 2.3 and 3.6, respectively. The results demonstrate that changes in disease state and to a lesser extent claw region and age are accompanied by alterations in the RNA expression of several cytokines, growth factors and receptors present in the normal claw.