Abrogation of Fam20c altered cell behaviors and BMP signaling of immortalized dental mesenchymal cells

Abstract

FAM20C mutations compromise the mineralization of skeleton and tooth in both human and mouse. Putatively, the mineralization disorder is attributed to the elevated fibroblast growth factor 23 (FGF23), which reduced the serum phosphorus by suppressing the reabsorption of phosphorus in kidney. Besides the regulation on systemic phosphorus homeostasis, FAM20C was also implicated to regulate cell behaviors and gene expression through a cell-autonomous manner. To identify the primary effects of Fam20c on dental mesenchymal cells, mouse Fam20c-deficient dental mesenchymal cells were generated by removing the floxed alleles from the immortalized mouse Fam20c dental mesenchymal cells with Cre-expressing lentivirus. The removal of Fam20c exerted no impact on cell morphology, but suppressed the proliferation and mobility of the dental mesenchymal cells. Fam20c deficiency also significantly reduced the expression of Osterix, Runx2, type I Collagen a 1 (Col1a1), Alkaline phosphatase (Alpl) and the members of the small integrin-binding ligand, N-linked glycoprotein (SIBLING) family, but increased Fgf23 expression. Consistently, the in vitro mineralization of Fam20c-deficient dental mesenchymal cells was severely disabled. However, supplements of the non-collagenous proteins from wild type rat dentin failed to rescue the compromised mineralization, suggesting that the roles of FAM20C in tooth mineralization are more than phosphorylating local matrices and regulating systemic phosphorus metabolism. Moreover, the down-regulated BMP signaling pathways in the Fam20c deficient dental mesenchymal cells revealed that the kinase activity of FAM20C might be required to maintain BMP signaling. In summary, our study discloses that Fam20c indeed regulates cell behaviors and cell signaling pathway in a cell-autonomous manner.

In‐depth investigation of FAM20A insufficiency effects on deciduous dental pulp cells: Altered behaviours, osteogenic differentiation, and inflammatory gene expression

“…We observed that reduced FAM20A is associated with compromised cellular behaviours, including impaired proliferation, attachment, spreading, migration, and colony formation in DDP. These findings align with previous findings showing that Fam20c deficiency in mouse dental mesenchymal cells resulted in suppressed proliferation, mobility, and wound healing (Liu, Zhou, et al., 2018). Similarly, FAM20C knockout in osteoblast cell lines presented reduced cell proliferation, adhesion, migration, and colony (Geng et al., 2022; Liu, Zhang, et al., 2018; Tagliabracci et al., 2015).…”

Weighted gene correlation network analysis reveals novel biomarkers associated with mesenchymal stromal cell differentiation in early phase

“…PRKCA, another hub gene, was demonstrated to regulate bone architecture and osteoblast activity (Galea et al, 2014). FAM20C encodes a family member of secreted protein kinases, which can bind calcium and phosphorylate proteins involved in bone mineralization (Liu et al, 2018). RBPJ, a primary nuclear mediator of Notch signaling, has also been associated with osteogenesis (S3) (Wang et al, 2010).…”

The ABCs of the atypical Fam20 secretory pathway kinases

“…Indeed, a large body of literature, focusing on conditional tissue-specific knockout mice and cell models, reports the roles of Fam20C in promoting biomineralization including the growth and development of osteoblasts, osteoclasts, bone, dentin, and enamel ( Fig. 5 ) ( 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 ).…”