Molecular mechanisms of intermuscular bone development in fish: a review

Abstract

Intermuscular bones (IBs) are slender linear bones embedded in muscle, which ossify from tendons through a process of intramembranous ossification, and only exist in basal teleosts. IBs are essential for fish swimming, but they present a choking risk during human consumption, especially in children, which can lead to commercial risks that have a negative impact on the aquaculture of these fish. In this review, we discuss the morphogenesis and functions of IBs, including their underlying molecular mechanisms, as well as the advantages and disadvantages of different methods for IB studies and techniques for breeding and generating IB-free fish lines. This review reveals that the many key genes involved in tendon development, osteoblast differentiation, and bone formation, e.g., scxa , msxC , sost , twist , bmps , and osterix , also play roles in IB development. Thus, this paper provides useful information for the breeding of new fish strains without IBs via genome editing and artificial selection.

Transcriptomic Analysis Provides Insights to Reveal the bmp6 Function Related to the Development of Intermuscular Bones in Zebrafish

“…Many signaling pathways are involved in bone regeneration, such as the Wnt/β-catenin pathway, BMP/Smad pathway, Hedgehog pathway, and Notch pathway ( Yan and Alman, 2009 ). The key signaling pathway involved in the IB developmental stages (S1–S4) includes cyclic adenosine monophosphate (cAMP), phosphatidylinositol 3′-kinase-Akt (PI3K-Akt), mitogen-activated protein kinase (MAPK), tumor necrosis factor (TNF) signaling, and vascular endothelial growth factor (VEGF) signaling ( Wan et al, 2016 ; Nie C.-H. et al, 2019 ; Li et al, 2021 ). P53 inhibits the expression of OSX (Sp7) to prevent bone development and osteoblast differentiation ( Sinha and Zhou, 2013 ).…”

“…IBs are small, hard-boned spicules located in the muscle tissue on both sides of the vertebrae; they mainly exist in the myosepta of lower teleosts ( Li et al, 2013 ; Nie C.-H. et al, 2019 ). IBs are difficult to remove, so they may be dangerous when consumed and are not conducive to the processing of aquatic products ( Li et al, 2021 ). Therefore, IBs have been recognized as a noteworthy feature in aquaculture breeding programs because of their negative effect on the edibleness and economic value of fishes ( Nie C. H. et al, 2019 ).…”

“…It is widely accepted that IBs arise undergoing intramembranous ossification of tendons in the myoseptum, in which mesenchymal cells directly differentiate into osteoblasts and begin to ossify ( Nie C.-H. et al, 2019 ). Omics studies showed that IB development involved many pathways, such as Wnt pathway, TGF-β pathway, MAPK, calcium signaling, thyroid hormone signaling, hedgehog signaling, TNF signaling, NF-kappa B pathway, and osteoclast differentiation( Li et al, 2021 ). Genes that may influence IB development include sxca , msxC , sost , and bmps (bone morphogenetic proteins).…”

Genetic regulation of injury-induced heterotopic ossification in adult zebrafish

“…Intermuscular bones form an integral part of the skeletal system in teleost fish. They are located in the myosepta on both sides of the vertebrae and considered to develop via intramembranous ossification of myoseptal tendons without undergoing a cartilaginous phase ( Li et al, 2021 ; Nie et al, 2019 ). In most teleost fish, there are three sets of intermuscular bones: epineurals, epicentrals and epipleurals, attaching ligamentously to neural, central and hemal arches or ribs, respectively ( Nie et al, 2019 ).…”

Role of p53 in promoting BMP9‑induced osteogenic differentiation of mesenchymal stem cells through TGF‑β1

“…p53 is also present in some newly discovered biological processes, such as ferroptosis (39,40). In terms of osteogenesis, several researchers have identified a negative regulatory effect of p53 on osteoblast differentiation, whereas some others suggested that mutations in p53 can increase osteoblast differentiation (41,42). The present study found that p53 was expressed in all MSCs tested and overexpression of p53 enhanced the potential of BMP9 induced osteogenic differentiation, while suppression of p53 decreased the expression level of early, intermediate, and late osteogenic markers, whereas p53 alone had no significant effect on MSCs differentiation in this study.…”