Effect of Neurotrophin‐4/5 on Bone/Cementum‐Related Protein Expressions and DNA Synthesis in Cultures of Human Periodontal Ligament Cells

Abstract

We studied neurotrophins (NTs) as signaling molecules for periodontal tissue regeneration and showed that nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) modulate the proliferation and differentiation of human periodontal ligament (HPL) cells in vitro. The purpose of this study was to investigate whether NT-4/5 also has the ability to regulate the function of HPL cells. mRNA expressions of NT-4/5 and its high-affinity tyrosine kinase receptor (trk)B were analyzed in HPL cells by reverse transcription-polymerase chain reaction. We examined how NT-4/5 regulates the mRNA expression of bone/cementum-related proteins (alkaline phosphatase [ALPase], osteopontin [OPN], osteocalcin [OC], and bone morphogenetic protein [BMP]-2) in cultures of HPL cells. Moreover, the effects of NT-4/5 on calcification, the production of OPN and OC, and DNA synthesis in HPL cells were examined. NT-4/5 and trkB mRNA were expressed in HPL cells. NT-4/5 elevated the mRNA levels of ALPase, OPN, OC, and BMP-2 and the syntheses of OPN, OC, and DNA in HPL cells. PD98059, an extracellular signal-regulated kinase (ERK) inhibitor, obviated the increase in the mRNA levels of ALPase, OPN, OC, and BMP-2. NT-4/5 increased the levels of phosphorylated ERK1/2. Furthermore, NT-4/5 enhanced the amount of mineral deposits in cultures of HPL cells. NT-4/5, as well as BDNF and NGF, is suggested to play a role in the regulation of function of periodontal ligament cells.