SialEXO® 23 in a Study of Osteoclast Fusion

In a recent paper from Johns Hopkins University School of Medicine in Baltimore, removal of sialic acids from toll-like receptor 2 using SialEXO 23 was found to inhibit osteoclast fusion. These new findings in osteoclast recognition signaling are important for understanding the pathogenesis of different skeletal disorders, also showcasing the versatility of Genovis SmartEnzymes!
 

Bone is a dynamic tissue that is constantly being broken down and restructured. Osteoclasts are large, multinucleated cells that are responsible for the dissolution and absorption of bone. The need for cell fusion in osteoclast formation has been studied for a long time, and several fusogenic molecules have been identified. However, the mechanisms behind the initiation of this cell fusion during osteoclast formation are still unknown.
 
Sialylation is mediated by sialyltransferases, which catalyzes the transfer of a sialic acid moiety to various acceptors in different linkages. Sialic acids are attached to galactose or N-acetylgalactosamine units via α2,3- or α2,6-linkages, and sialylated glycoconjugates are involved in several cellular events, including cell adhesion and viral fusion. Sialic acids are recognized by sialic acid-binding immunoglobulin-type lectins (Siglecs) that are mainly found on the surface of immune-related cells. Increases in sialic acid are associated with different skeletal diseases and blockade of sialic acids has been shown to efficiently suppress tumor growth.
 
In this paper, the molecular mechanisms behind the cell recognition that initiates osteoclast fusion were investigated. It was found that toll-like receptor 2 (TLR2) worked as a Siglec15 receptor. The SmartEnzyme SialEXO® 23 – an α2,3-specific sialidase – was used to remove sialic acids from TLR2, and the effects of the desialylation were studied. Interestingly, removal of the sialic acids from TLR2 using was found to disable the Siglec15 cell recognition and inhibit osteoclast fusion. Taken together, these new findings in osteoclast recognition signaling are important for understanding the pathogenesis of different skeletal disorders.
 

SialEXO 23 is an α2,3-specific sialidase that desialylates both O- and N-glycosylated proteins within one hour, and it hydrolyzes sialic acids under native conditions.
 

Reference

Dou et al., 2022. Sialylation of TLR2 initiates osteoclast fusion. Bone Research. https://doi.org/10.1038/s41413-022-00186-0.

SialEXO®23 – Hydrolysis of α2,3-linked sialic acids