RRC ID 42129
Author Yoshizawa T, Takizawa F, Iizawa F, Ishibashi O, Kawashima H, Matsuda A, Endo N, Kawashima H.
Title Homeobox protein MSX2 acts as a molecular defense mechanism for preventing ossification in ligament fibroblasts.
Journal Mol Cell Biol
Abstract Ligaments and tendons are comprised of tough yet flexible connective tissue. Little is known, however, about the precise characteristics of the cells in ligaments and tendons due to the absence of specific markers and cell lines. We recently reported a periodontal ligament cell line, PDL-L2, with suppressed Runx2/Osf2 transcriptional activity and an inability to form mineralized nodules. The present study demonstrates that the homeobox protein Msx2 is a key factor in suppressing those two functions. Msx2 colocalizes with Runx2/Osf2 and suppresses its activity cooperatively, acting with another corepressor, TLE1, as a complex to recruit histone deacetylase 1 activity. Reverse transcription-PCR and in situ hybridization demonstrated that Msx2 expression is higher in periodontal ligament and tendon cells than in osteoblasts. Stable reduction of Msx2 expression in PDL-L2 cells induces osteoblastic differentiation, thereby causing matrix mineralization. Conversely, stable, forced Msx2 expression in MC3T3-E1 cells prevented osteoblast differentiation and matrix mineralization. Msx2-induced suppression of osteoblast differentiation was repressed by bone morphogenetic protein 2. In addition, Msx2 was downregulated in a symptom- and calcification-dependent manner at the affected region in patients with ossification of the posterior longitudinal ligament. Our findings indicate that Msx2 plays a central role in preventing ligaments and tendons from mineralizing.
Volume 24(8)
Pages 3460-72
Published 2004-4-1
DOI 10.1128/MCB.24.8.3460-3472.2004
PMID 15060165
PMC PMC381680
MeSH Aged Animals Bone Morphogenetic Protein 2 Bone Morphogenetic Proteins / metabolism Cell Differentiation / physiology* Cell Line Co-Repressor Proteins Core Binding Factor Alpha 1 Subunit Culture Techniques DNA-Binding Proteins / genetics DNA-Binding Proteins / metabolism* Female Fibroblasts / cytology Fibroblasts / physiology* Gene Expression Regulation Homeodomain Proteins / genetics Homeodomain Proteins / metabolism* Humans Ligaments / cytology* Ligaments / physiology* Male Mice Mice, Inbred C57BL Middle Aged Neoplasm Proteins / genetics Neoplasm Proteins / metabolism Nuclear Proteins / metabolism Ossification, Heterotopic* Osteogenesis* Recombinant Fusion Proteins / metabolism Recombinant Proteins Repressor Proteins* Tendons / cytology Tendons / physiology Transcription Factors / genetics Transcription Factors / metabolism Transcription, Genetic Transforming Growth Factor beta*
IF 3.611
Times Cited 92
Human and Animal Cells C2C12(RCB0987) MC3T3-E1(RCB1126)