Bioelectricity最新文献

Background: The regenerating zebrafish fin skeleton is comprised of multiple bony fin rays, each made of alternating bony segments and fin ray joints. This pattern is regulated by the gap junction protein Connexin43 (Cx43), which provides instructional cues to skeletal precursor cells (SPCs). Elevated Cx43 favors osteoblast differentiation and disfavors joint forming cell differentiation. The goal of this article is to test if retinoic acid (RA) contributes to the regulation of cx43 expression.

Materials and methods: Functional studies inhibiting the RA-synthesizing enzyme Adh1a2 were evaluated using in situ hybridization to monitor gene expression and with measurements of the length of fin ray segments to monitor impacts on SPC differentiation and joint formation.

Results: Aldh1a2-knockdown leads to reduced expression of cx43 and increased expression of evx1, a gene required for joint formation. Additionally, inhibition of Aldh1a2 function leads to short fin ray segments. We also find evidence for synergy between aldh1a2 and cx43, suggesting that these genes function in a common molecular pathway to regulate joint formation.

Conclusions: The role of RA is to promote cx43 expression in the regenerating fin to regulate joint formation and the length of bony fin ray segments. We suggest that RA signaling must coordinate with additional pathways that also regulate cx43 transcription.

The presence of gap junction intercellular communication structures in bone cells has been known since the early 1970s, further confirmed by Doty and Marotti at the structural level in the 1980-1990s. Work by Civitelli, Donahue, and others showed the expression of Cx43 at the mRNA and protein levels in all bone cell types: osteoclasts (bone resorbing cells), osteoblasts (bone forming cells), and osteocytes (mature osteoblasts embedded in the bone matrix that regulate the function of both osteoclasts and osteoblasts). While Cx45, Cx46, and Cx37 were also shown to be expressed in bone cells, most studies have focused on Cx43, the most abundant member of the connexin (Cx) family of proteins expressed in bone. The role of Cx43 has been shown to be related to the formation of gap junction intercellular channels, to unopposed hemichannels, and to channel independent functions of the molecule. Cx43 participates in the response of bone cells to pharmacological, hormonal, and mechanical stimuli, and it is involved in the skeletal phenotype with old age. Human and murine studies have shown that mutations of Cx43 lead to oculodentodigital dysplasia and craniometaphyseal dysplasia, both conditions associated with abnormalities in the skeleton. However, whereas substantial advances have been made on the skeletal role of Cx43, further research is needed to understand the basis for the effects of mutated Cx43 and potential ways to prevent the effects of these mutations on bone.

Mutations of lens connexins are linked to congenital cataracts. However, the role of connexin mutations in the development of age-related lens opacification remains largely unknown. Here, we present a focused review of the literature on lens organization and factors associated with cataract development. Several lines of evidence indicate that disturbances of the lens circulation by dysfunctional connexin channels, and/or accumulation of protein damage due to oxidative stress, are key factors in cataract development. Phosphorylation by protein kinase A improves the permeability of connexins channels to small molecules and mitigates the lens clouding induced by oxidative stress. We conclude (1) that connexin channels are central to the lens circulation and (2) that their permeability to antioxidant molecules contributes to the maintenance of lens transparency.