Fibroblast Activation Protein Is Expressed by Altered Osteoprogenitors and Associated to Disease Burden in Fibrous Dysplasia

TL;DR

This study shows that Fibroblast Activation Protein (FAPα) is elevated in fibrous dysplasia (FD) and may serve as a useful biomarker or drug target for the condition.

Contribution

The study identifies FAPα as a novel biomarker and potential therapeutic target for fibrous dysplasia.

Findings

FAP genetic expression is increased in FD tissue and cells.

FAPα levels in plasma are higher in FD patients than in healthy donors.

FAPα levels correlate with the severity of skeletal disease in FD patients.

Abstract

Fibrous dysplasia (FD) is a mosaic skeletal disorder involving the development of benign, expansile fibro-osseous lesions during childhood that cause deformity, fractures, pain, and disability. There are no well-established treatments for FD. Fibroblast activation protein (FAPα) is a serine protease expressed in pathological fibrotic tissues that has promising clinical applications as a biomarker and local pro-drug activator in several pathological conditions. In this study, we explored the expression of FAP in FD tissue and cells through published genetic expression datasets and measured circulating FAPα in plasma samples from patients with FD and healthy donors. We found that FAP genetic expression was increased in FD tissue and cells, and present at higher concentrations in plasma from patients with FD compared to healthy donors. Moreover, FAPα levels were correlated with skeletal disease burden in patients with FD. These findings support further investigation of FAPα as a potential imaging and/or biomarker of FD, as well as a pro-drug activator specific to FD tissue.

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