Lactoferricin Enhances BMP7-Mediated Anabolism in Bovine Intervertebral Disc Cells

Kim, JS; +Im, H-J +Department of Biochemistry, Orthopedic Surgery, Internal Medicine Rush University Medical Center, Chicago, IL60612 +Hee-Jeong [email protected] INTRODUCTION To date, research has shown that progressive breakdown of the extracellular matrix (ECM) is closely associated with disc degeneration. Therefore, biological treatments capable of promoting ECM repair and regeneration have been considered, and clinical trials are underway [1]. Bone morphogenetic protein-7 (BMP7 or OP-1), a member of the transforming growth factor-β (TGF-β) superfamily, was found to exert potent anabolic effects on chondrocyte differentiation and metabolism via Smad 1/5/8 signaling pathway [2]. But BMP7 induces noggin, through a negative feedback. Noggin, a well known inhibitor of BMP activity, is a vital molecule involved in cephalogenesis and skeletogenesis in a variety of species [3, 4]. Therefore, we hypothesized that noggin is capable of inhibiting BMP7-mediated anabolic effects in bovine disc cells. Lactoferricin (LfcinB), a peptide 25 amino acid residues, is acquired from lactoferrcin via proteolysis by acidic pepsin. LfcinB possesses strong antimicrobial, antivirus, anti-oxidant, anti-cancer activities [5]. Previously, we reported the anabolic and anti-catabolic property of LfcinB in bovine IVD cells. The aim of the present study is to determine the potential of BMP7 in combination with LfcinB to retard the progression of IVD degeneration. Specifically, we studied the effect of this on bovine IVD homeostasis compared to individual treatments through assessing PG accumulation, PG synthesis, and noggin expression, as well as analyzing the mechanisms by which LfcinB may potentiate BMP7 activity.