MACF1 deficiency suppresses tooth mineralization through IGF1 mediated crosstalk between odontoblasts and ameloblasts

Tooth mineralization is a ubiquitous and tightly regulated process involving complicated interactions between dental epithelium and mesenchyme.Key molecules in tooth mineralization remain poorly identified.Microtubule actin cross-linking factor 1(MACF1)is a spectraplakin protein that plays pivotal roles in the brain,muscle,lung,and bone developmental process.^(1-3) To study the specific functions of MACF1 in bone formation,we established Macf1 conditional knockout mice using the Cre-LoxP system driven by Osxterix promoter(Osx-Cre;Macf1^(f/f)).^(2) Not surprisingly,Osx-Cre;Macf1^(f/f) mice displayed the phenotypes of delayed ossification and decreased bone mass.Moreover,the OsxCre;Macf1^(f/f) mice unexpectedly showed a white and opaque appearance of incisors,contrary to the normal yellowbrown and transparent incisors.Since Osxterix is expressed in dental mesenchyme during tooth development,the abnormal tooth appearance might imply a new function of MACF1 in odontoblasts,or even ameloblasts.Therefore,the present study aimed to investigate the role of MACF1 during tooth development.

An integrated genome-wide analysis identifies HUR/ELAVL1 as a positive regulator of osteogenesis through enhancing theβ-catenin signaling activity

Osteoporosis is a prevalent multifactorial bone disease with a strong genetic contribution.The heritability of traits that contribute to osteoporosis(bone mass,bone mineral density(BMD),bone size,bone loss and fractures)ranges from 50 to 85%,suggesting that a comprehensive understanding of the genetic basis may help identify new therapeutic targets.1 However,the genetic characteristics remain obscure,and the existing drug targets are associated with various challenges.Numerous studies have demonstrated that high-throughput sequencing data analysis is fruitful for identifying novel targets of human diseases.2 We therefore integrated GWAS and transcriptome analyses through Multi-marker Analysis of GenoMic Annotation(MAGMA)and weighted gene co-expression network analysis3(WGCNA)to identify new network modules and potential therapeutic genes for osteoporosis.As an illustration,the flow chart presenting the process of the present study was shown in Figure S1.

Microtubule actin crosslinking factor 1 functions as a novel therapeutic target in lung metastasis of osteosarcoma

Lung metastasis is the primary cause of death in osteosarcoma(OS)patients.1 A better understanding of the molecular mechanisms underlying OS tumorigenesis and metastasis is urgently needed to identify therapeutic targets.Microtubule actin crosslinking factor 1(MACF1),which belongs to the spectraplakin family of cytoskeletal crosslinking proteins,2 is critical for cell migration and polarization due to its regulation of the cytoskeleton.Recently,MACF1 was indicated to be involved in the metastatic invasion of some human cancers,3 but the function of MACF1 in OS is still unclear.