Osteoblast-derived acetylcholinesterase: A novel mediator of cell-matrix interactions in bone?

The adhesive interactions that occur between bone cells and the developing matrix during bone formation help guide coupled remodeling and the maintena nce of bone mass. Here, we provide evidence that acetylcholinesterase (AChE ) is a novel osteoblast-derived mediator of cell-matrix interactions in bon e. These findings complement an increasing body of evidence which suggests that AChE, in addition to its role in terminating cholinergic signaling, ma y be instrumental in regulating cellular differentiation and adhesion. We h ave shown, using RT-PCR, that osteosarcoma cell lines and primary cultures of osteoblasts express AChE mRNA, Expression appeared to be differentiation -dependent, and restricted to AChE splice variants containing the T subunit (exon 6), Immunofluorescent localization demonstrated that these osteoblas tic cells expressed protein for AChE with an intracellular vesicular distri bution. Immunohistochemistry on tissue sections confirmed AChE expression b y osteoblasts in vivo, and revealed the presence of AChE along cement lines , also identified by enzyme histochemistry, In vitro functional studies ind icated that osteoblast-like cells adhered specifically to and spread on ACh E substrates, but did not interact with butyrylcholinesterase, a closely re lated protein. Our evidence strongly implicates AChE as a novel bone matrix protein, capable of mediating cell-matrix interactions, and as such may be a principal participant in organized bone formation and the regulation of remodeling. (C) 1999 by Elsevier Science Inc. All rights reserved.