Role of Sostdc1 in skeletal biology and cancer

Abstract

Sclerostin domain-containing protein-1 (Sostdc1) is a member of the sclerostin family and encodes a secreted 28–32 kDa protein with a cystine knot-like domain and two N-linked glycosylation sites. Sostdc1 functions as an antagonist to bone morphogenetic protein (BMP), mediating BMP signaling. It also interacts with LRP6, mediating LRP6 and Wnt signaling, thus regulating cellular proliferation, differentiation, and programmed cell death. Sostdc1 plays various roles in the skin, intestines, brain, lungs, kidneys, and vasculature. Deletion of Sostdc1 gene in mice resulted in supernumerary teeth and improved the loss of renal function in Alport syndrome. In the skeletal system, Sostdc1 is essential for bone metabolism, bone density maintenance, and fracture healing. Recently, Sostdc1 has been found to be closely related to the development and progression of multiple cancer types, including breast, renal, gastric, and thyroid cancers. This article summarises the role of Sostdc1 in skeletal biology and related cancers to provide a theoretical basis for the treatment of related diseases.

Two opposing roles for Bmp signalling in the development of electrosensory lateral line organs

“…Sostdc1 (sclerostin domain-containing 1; also known as Wise, Ectodin) is a secreted antagonist of both the Bmp and Wnt pathways (Tong et al, 2022). Sostdc1 was 4.2-fold enriched in late-larval paddlefish operculum versus fin tissue (Modrell et al, 2017a).…”

“…In contrast, the pattern of Sostdc1 expression (Supplementary Figure S3) suggests its role may be more prominent during neuromast development. However, given the ability of Apcdd1 and Sostdc1 to inhibit both the Bmp and Wnt pathways (Tong et al, 2022; Vonica et al, 2020), we cannot be sure which of these pathway(s) either of these proteins may be antagonising during sterlet lateral line organ development.…”

“…Vwc2 was 4.5-fold lateral line-enriched (Modrell et al, 2017a), but ISH for this gene in sterlet was unsuccessful so it is not considered further. Sostdc1 (sclerostin domain-containing 1; also known as Wise, Ectodin) is a secreted antagonist of both the Bmp and Wnt pathways (Tong et al, 2022). Sostdc1 was 4.2-fold enriched in late-larval paddlefish operculum versus fin tissue (Modrell et al, 2017a).…”

The neocortical infrastructure for language involves region-specific patterns of laminar gene expression

“…For SOSTDC1 , there was markedly higher infragranular than supragranular expression in the superior temporal sulcus, while in the inferior frontal gyrus the expression level was similar in infragranular and supragranular layers (Figure 3C). SOSTDC1 encodes a secreted protein of the sclerostin family that functions as an antagonist to growth factors of the bone morphogenetic protein (BMP) family, and also affects Wnt signalling (41). The 72-gene set showed enrichments at FDR p<0.01 for thirteen biological processes defined in the Gene Ontology (42), most significantly for functions related to neuron projection/axon guidance, driven by the genes encoding signalling molecules NELL1, PTPRM, SLIT1 and SLIT2 (Supplementary Table 4) (43).…”