Endochondral bone formation occurs through progressive remodelling of a cartilage template into bone intramembranous bone formation occurs by mesenchymal condensation of osteoblasts. Bone is formed by evolutionarily conserved processes via either endochondral or intramembranous (dermal) ossification. ![]() Skeletal structures have a collagen-rich matrix that provides shape, organ protection, endocrine, and locomotive functions to the organism. The vertebrate skeleton is composed of non-mineralised cartilage and mineralised bone, enamel, and dentine structures. Despite the many differences between scale and endoskeletal developmental processes, we also show that zebrafish scales express an evolutionarily conserved sub-population of genes that are relevant to human skeletal disease. We show that scales have a strong osteogenic expression profile comparable to other elements of the dermal skeleton, enriched in genes that favour collagen matrix growth. Zebrafish mutants of two human orthologues that were robustly associated with height ( COL11A2, P=6× 10 −24) or eBMD ( SPP1, P=6× 10 −20) showed both exo- and endo- skeletal abnormalities as predicted by our genetic association analyses col11a2 Y228X/Y228X mutants showed exoskeletal and endoskeletal features consistent with abnormal growth, whereas spp1 P160X/P160X mutants predominantly showed mineralisation defects. The DEGs were also enriched for human orthologues associated with polygenetic skeletal traits, including height ( P< 6× 10 −4), and estimated bone mineral density (eBMD, P< 2× 10 −5). Hypergeometric tests involving monogenetic skeletal disorders showed that DEGs were strongly enriched for human orthologues that are mutated in low bone mass and abnormal bone mineralisation diseases ( P< 2× 10 −3). These were enriched for extracellular matrix, ossification, and cell adhesion pathways, but not in enamel or dentin formation processes indicating that scales are reminiscent to bone. We defined the transcriptomic profiles of ontogenetic and regenerating scales of zebrafish and identified 604 differentially expressed genes (DEGs). Therefore, we performed transcriptomic analysis to determine gene networks and their pathways involved in dermal scale regeneration. Processes promoting de novo matrix formation and mineralisation initiated during scale regeneration are poorly understood. When removed, an ontogenetic scale is quickly replaced following differentiation of the scale pocket-lining cells that regenerate a scale. Each scale is a mineralised collagen plate that is decorated with both matrix-building and resorbing cells. Scales have been mostly lost during evolution of terrestrial vertebrates whilst bony fish have retained a mineralised dermal skeleton in the form of fin rays and scales. One year of seal oil omega-3 nutrition therapy increased blood omega-3s, while small nerve fiber regeneration appears to be related to baseline omega-3 status.Scales are mineralised exoskeletal structures that are part of the dermal skeleton. 1.34☐.40%, p=0.009).The change in these variables was not different between responders and non-responders (p>0.05). At baseline, responders had higher total omega-3 (4.38☑.35% vs. At 12-months, omega-3 nutrition therapy increased group mean plasma EPA by 185%, DPA by 29%, DHA by 79% (p0% and 9(22%) with a clinically significant loss of CNFL >-6%. At baseline, participants with DSP had lower DHA concentration compared to those without (1.73☐.89% vs. The 40 participants (53% female) had mean±SD age 48☑4 years, body mass index 28.1±5.8 kg/m2, diabetes duration 27☑8 years and 23(59%) had DSP. Plasma PUFAs were measured at 0, 4, 8 and 12-months. ![]() The primary outcome was the 1-year change in corneal nerve fiber length (CNFL) measured by in vivo corneal confocal microscopy, with sensory and nerve conduction measures as secondary outcomes. Forty individuals with T1D participated in a 12-month single-arm open label study of seal oil omega-3 (10 mL/d 750 mg EPA, 560 mg DPA acid, and 1,020 mg DHA). ![]() It is unclear if baseline omega-3s relate to the presence of diabetic sensorimotor polyneuropathy (DSP) or nerve regeneration. We have recently demonstrated that omega-3 nutrition therapy is associated with small nerve fiber regeneration in individuals with type 1 diabetes (T1D).
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