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Exploring the role of osteopontin after spinal cord injury in adult zebrafish
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A Spinal cord injury (SCI) is a complex condition affecting 26.5 individuals per
million, with Portugal having the highest incidence rate in Europe. SCI results in
significant physical impairment, leading to high costs associated with medical care and
rehabilitation. Moreover, it profoundly impacts the quality of life and independence of
affected individuals.
In mammals, SCI often causes severe and permanent symptoms due to the
limited regenerative capacity of the Central Nervous System (CNS). In contrast, zebrafish
possess remarkable regenerative abilities, allowing for complete recovery after SCI.
However, the vascular response - an essential process impaired in mammalian SCI - has
been largely overlooked in zebrafish research. Recent studies indicate that zebrafish
rapidly form and remodel blood vessels following SCI, restoring barrier function and
closely resembling uninjured vasculature. Macrophages, known for their angiogenic role
in other contexts, have emerged as potential regulators of spinal cord revascularisation.
Preliminary RNA sequencing data have shown early upregulation
of osteopontin (spp1) after SCI. Osteopontin is secreted by various cell types including
macrophages, modulates processes such as cell migration, proliferation, differentiation,
wound healing, and angiogenesis. The upregulation after injury suggests its involvement
in spinal cord repair, potentially influencing the vascular response.
In this study, we examined the expression of spp1 during spinal cord regeneration
in zebrafish at multiple time points post-injury. Our results reveal that spp1 expression
begins at 3 days post-injury (dpi), peaks at 7 dpi, and declines by 14 dpi. Further
analysis confirmed spp1 expression in macrophages and perivascular cells. However,
additional spp1+cell populations that do not correspond to these cell types may also play
a role, suggesting the involvement of other cell types in the SCI response. Despite these
findings, the precise function of Osteopontin in spinal cord regeneration remains unclear.
Understanding the role of Osteopontin is essential for elucidating tissu regeneration mechanisms after SCI and for exploring its potential therapeutic modulation in non-regenerative organisms.
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Spinal Cord Injuries Osteopontin Zebrafish