MEPE activated by furin promotes pulpal cell adhesion

Area of Science:

• Biochemistry
• Cell Biology
• Dentinogenesis

Background:

• Matrix extracellular phosphoglycoprotein (MEPE) is vital for bone and dentin metabolism.
• Post-translational modifications (PTMs) are essential for MEPE activation.
• MEPE is primarily expressed in osteoblasts, osteocytes, and odontoblasts.

Purpose of the Study:

• To investigate the hypothesis that furin proteolytically processes and activates MEPE in dental pulp.
• To identify the specific cleavage site and responsible enzyme for MEPE activation.

Main Methods:

• Western blotting to detect MEPE forms.
• Site-directed mutagenesis to alter the putative cleavage site.
• Expression of MEPE in furin-deficient cells (LoVo).

Main Results:

• MEPE exists in full-length and two cleaved forms, with cleavage at 146R↓147.
• Mutating the cleavage site abolished MEPE hydrolysis.
• MEPE was not cleaved in furin-deficient LoVo cells, implicating furin.
• The C-terminal fragment of MEPE promoted cell adhesion via an RGD motif.

Conclusions:

• Furin is a key enzyme responsible for the proteolytic processing and activation of MEPE.
• MEPE activation through furin cleavage during secretion from odontoblasts is important for dentinogenesis and pulpal homeostasis.
• The RGD motif in the MEPE C-terminal fragment suggests a role in cell adhesion during these processes.