OBIF, an osteoblast induction factor, plays an essential role in bone formation in association with osteoblastogenesis

Abstract

In vertebrate bone formation, the functional mechanisms of transcription factors in osteoblastic differentiation have been relatively well elucidated; however, the exact roles of cell-extrinsic molecules are less clear. We previously identified human and mouse Obif, an osteoblast induction factor, also known as Tmem119, which encodes a single transmembrane protein. OBIF is predominantly expressed in osteoblasts in mouse. While exogenous Obif expression stimulated osteoblastic differentiation, knockdown of Obif inhibits the osteoblastic differentiation of pre-osteoblastic MC3T3-E1 cells. In order to investigate an in vivo role of OBIF in bone formation, we generated Obif-deficient mice by targeted gene disruption. Analyses of micro-computed tomography (mCT) revealed that Obif ) ⁄ ) mice exhibit significantly reduced cortical thickness in the mid-shaft of the femur at postnatal day 14 (P14). Furthermore, progressive bone hypoplasia is observed after 8 weeks. The expression levels of osteoblast marker genes, Collagen 1a1, Osteopontin, Runx2, and Osterix, in the calvaria were decreased in Obif ) ⁄ ) mice at P4. These data indicate that Obif plays an essential role in bone formation through regulating osteoblastogenesis.

Upregulation and biological function of transmembrane protein 119 in osteosarcoma

“…32, 33, 34 TMEM119 promotes osteoblast differentiation by regulating the BMP2 pathway. 21, 22, 23, 24 We found that silencing TMEM119 expression significantly decreased the levels of TGF-β1, BMP2 and BMP7 proteins, and TGF-β exposure significantly rescued the inhibitory effects of TMEM119 siRNA on osteosarcoma cell migration and invasion. Furthermore, the promoting effects of TMEM119 overexpression on osteosarcoma cell migration and invasion were impaired by a TGF-β inhibitor (SB431542) or a BMP inhibitor (dorsomorphin).…”

“…8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18 TMEM119 has an important role in osteoblast differentiation by regulating the BMP2 pathway. 21, 22, 23, 24 However, the expression and roles of TMEM119 in bone cancer remain unclear. In this study, we identified TMEM119 as a potential oncogene in osteosarcoma based on analysis of publicly available datasets and clinical subjects as well as in in vitro and in vivo functional experiments.…”

“…19 Studies to date have reported that TMEM119 contributes to bone and testis development 20 as well as to osteoblast differentiation. 21, 22, 23, 24 As it has been suggested that osteosarcoma is caused by disruption of osteoblast differentiation, we hypothesized that TMEM119 may be involved in osteosarcoma tumorigenesis. In the current study, we determined the expression patterns of TMEM119 at both the mRNA and protein levels in osteosarcoma tissues and revealed the clinical value of its aberrant expression in this disease.…”

Decoding the transcriptome of atherosclerotic plaque at single-cell resolution

“…FBN1 (ECM component) is strongly correlated with TGFBR3, SEMA3C and CD248 (modulators of EMT-like processes) 67–69 . Interestingly, this group of cells co-expresses IGSF10 , a marker of early osteochondroprogenitor cells 70 , TMEM119 (bone formation and mineralization; promotes differentiation of myeloblasts into osteoblasts) 71,72 and WNT11 (bone formation) 73 (Extended Data Fig. 7a).…”

Osteogenic changes in kidneys of hyperoxaluric rats

“…BMP2 induces OPN expression through RUNX2. [93] RUNX2 is also involved in transcriptional regulation of many other proteins involved in mineralization such as matrix-GLA protein (MGP),[94] collagen1a1,[95, 96] osteocalcin,[97] and fibronectin. [92] BMP2 and RUNX2 induced calcification is modulated through NADPH oxidase mediated production of reactive oxygen species.…”