Fibromodulin, a Multifunctional Matricellular Modulator

Fibromodulin (FMOD) is an archetypal member of the class II small leucine-rich proteoglycan family. By directly binding to extracellular matrix structural components, such as collagen and lysyl oxidase, FMOD regulates collagen cross-linking, packing, assembly, and fibril architecture via a multivalent interaction. Meanwhile, as a pluripotent molecule, FMOD acts as a ligand of various cytokines and growth factors, especially those belonging to the transforming growth factor (TGF) beta superfamily, by interacting with the corresponding signaling molecules involved in cell adhesion, spreading, proliferation, migration, invasion, differentiation, and metastasis. Consequently, FMOD exhibits promigratory, proangiogenic, anti-inflammatory, and antifibrogenic properties and plays essential roles in cell fate determination and maturation, progenitor cell recruitment, and tissue regeneration. The multifunctional nature of FMOD thus enables it to be a promising therapeutic agent for a broad repertoire of diseases, including but not limited to arthritis, temporomandibular joint disorders, caries, and fibrotic diseases among different organs, as well as to be a regenerative medicine candidate for skin, muscle, and tendon injuries. Moreover, FMOD is also considered a marker for tumor diagnosis and prognosis prediction and a potential target for cancer treatment. Furthermore, FMOD itself is sufficient to reprogram somatic cells into a multipotent state, creating a safe and efficient cell source for various tissue reconstructions and thus opening a new avenue for regenerative medicine. This review focuses on the recent preclinical efforts bringing FMOD research and therapies to the forefront. In addition, a contemporary understanding of the mechanism underlying FMOD's function, particularly its interaction with TGF beta superfamily members, is also discussed at the molecular level to aid the discovery of novel FMOD-based treatments.

Automated summary

Fibromodulin (FMOD) is a multifunctional molecule that plays important roles in extracellular matrix regulation, cytokine and growth factor binding, and tissue regeneration. It has the potential to be used as a therapeutic agent for various diseases and as a marker and target for cancer diagnosis and treatment. Moreover, it can reprogram cells for regenerative medicine applications.