The bisphosphonate etidronate reduced vertebral fusions in zebrafish lacking <code>col9a1b</code>

The bisphosphonate etidronate reduced vertebral fusions in zebrafish lacking col9a1b

On July 28, Communications Biology published a study of zebrafish larvae in which col9a1b, a gene encoding part of collagen IX, had been knocked out. Ten days of etidronate treatment reduced the number of vertebral fusions in these larvae.

In zebrafish, the tissues surrounding the notochord, a flexible rod that runs along the body, absorb mechanical loads in a manner similar to the mammalian intervertebral disc. In a 2021 study, the same group described age-related changes in these tissues. The new model shows what happens earlier: collagen IX helps bind together the fibers that form the tissue's supporting framework.

The mutant larvae developed the usual number of segments that would later form vertebrae, but the segments were often misshapen. The notochord sheath then became thinner and lost its normal organization because its collagen and elastin layers failed to form a continuous structure. The gene entpd5 was more active in the regions that would later become the spaces between vertebrae. Its protein helps release phosphate for the formation of mineral crystals. The tissue between the vertebrae became mineralized, and the vertebrae later fused.

The authors began treatment on day 15 of development, with ten fish in each group. Etidronate binds to calcium phosphates and inhibits the nucleation and growth of crystals. After ten days, the mutants therefore had fewer vertebral fusions. Ibuprofen, an anti-inflammatory drug used by the authors to test the role of inflammation, did not change the number of fusions.

These interventions help establish the sequence of events in this genetic model. First, the collagen framework of the notochord is disrupted. The tissue between the vertebrae then becomes mineralized, after which the vertebrae fuse. Inhibiting crystal formation reduced the number of fusions.