MMP-13(Matrix MetalloProteinase 13) expression might be an indicator for increased ECM remodeling and early signs of vertebral compression in farmed Atlantic salmon (Salmo salarL.)

Abstract

SummaryVertebral body compression is a common problem in commercial farming of Atlantic salmon. Although risk factors, such as vaccination and malnutrition, have been identified, the etiology is largely unknown. Histological studies of Atlantic salmon have shown that in a compressed deformity (platyspondyly) the length of the compact bone is reduced while the notochord start to form atypical chrondrogenic structures. In mammals, similar remodeling activities have been linked to inflammatory processes in the tissue. Hence, we wanted to investigate whether the compressed vertebrae in Atlantic salmon showed presence of local (IL-1b, TNF-a1), systemic (IgM) and chronic (MMP-13, MMP-9) immune responses (measured with quantitative PCR). Unvaccinated groups of Atlantic salmon that would later develop high or low prevalence of vertebral compression during on-growth in seawater were sampled at seawater transfer, and 3 and 6 weeks after seawater transfer. In addition, compressed and normal vertebrae from the high deformity prevalence group were sampled 44 weeks after transfer to seawater. MMP-13 was significantly up-regulated in the group that developed a high prevalence of deformity, and also significantly up-regulated in compressed vertebrae, 44 weeks after seawater transfer. In compressed vertebrae, MMP-13 was equally up-regulated in the notochord, compact bone and trabecular bone. The results of the present study suggest that MMP-13 may serve as an early indicator for bone remodeling which may lead to vertebral compression, and that there is a relationship between the development of vertebral compression and increased remodeling activities in farmed Atlantic salmon.

Skeletal anomalies in reared European fish larvae and juveniles. Part 2: main typologies, occurrences and causative factors

“…The process underlying temperature‐induced anomalies in salmon is only hypothesized by Wargelius et al . (): in fish reared at higher temperature, in the compressed vertebrae, notochord, compact and trabecular bone, MMP13 was significantly upregulated, 44 weeks after seawater transfer. Ytteborg et al .…”

“…Among the main risk factors invoked for the onset of spinal anomalies, in contrast to those reported in non‐salmonid species, temperature seems to be the most potent (Wargelius et al . ), together with smoltification timing (underyearlings instead of yearlings), vaccination and dietary phosphorus deficiency, even if the reproducibility of induction of these anomalies by these factors has not always succeeded in laboratory conditions (Gil Martens ).…”

Vertebral deformities in farmed Atlantic salmon (Salmo salar L.) - etiology and pathology

“…This shows that regular mechanical load has a positive effect on bone development, as reported for cichlids (Huysseune et al., 1994) and for mammals (Boyde, 2003). Wargelius et al. (2010a) found that a group of postsmolts with a high mRNA expression level in vertebral bone of MMP‐13 (Matrix MetalloProteinase 13), which codes for a protein belonging to a family of proteins involved in the degradation of the extracellular matrix, developed a high percentage of fish with compressions later on.…”

“…The aggravation of deformities involves the increase of the number of deformed vertebral bodies adjacent to an already existing location of malformed and fused vertebral bodies (Witten et al., 2006; Fjelldal et al., 2007a). There appears to be a delay of several weeks between the induction and the development of a deformity (Wargelius et al., 2010a; Grini et al., 2011). The expression level of several genes is different in deformed compared to normal vertebrae; collagen type XI a1 gene is down‐regulated in the compact but not in the trabecular bone (Wargelius et al., 2010b) and MMP‐13 is up‐regulated in both compact and trabecular bone of compressed vertebrae (Wargelius et al., 2010b).…”

Four stages characterizing vertebral fusions in Atlantic salmon

“…However, cellular and molecular events during pathological bone development in salmon have been little described and only a few studies have been published (e.g. Wargelius et al., 2010a,b; Ytteborg et al., 2010a,b,c). Our group recently finished a comprehensive study on temperature induced vertebral fusions in Atlantic salmon, where we described various stages of pathological development using molecular tools.…”