The transcription factor early B‐cell factor 1 regulates bone formation in an osteoblast‐nonautonomous manner

Zee, Tiffany; Boller, Sören; Győry, Ildikó; Makinistoglu, Munevver Parla; Tuckermann, Jan; Grosschedl, Rudolf; Karsenty, G.

doi:10.1016/j.febslet.2013.01.049

Cited by 12 publications

(7 citation statements)

References 21 publications

(29 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Bone marrow from 18-and 90-wk-old Prx1-Cre;Ebf1 f/f mice showed no gross hematopoietic or bone abnormalities (Supplemental Fig. S5A-E), consistent with previous studies of mice deficient for Ebf1 exhibiting a subtle or no skeletal phenotype (Hesslein et al 2009;Zee et al 2013). Histological analysis of femurs in newborn and 1-wk-old Prx1-Cre;Ebf1 f/f Ebf3 f/f ;CXCL12-GFP mice in which Ebf1 and Ebf3 were inactivated in mesenchymal cells, including CAR cells, revealed that although the trabecular bone mass was somewhat increased, bone marrow cavities were formed (Fig.…”

Section: Car Cells Exhibiting a Normal Morphology Are Present But Hssupporting

confidence: 90%

Stem cell niche-specific Ebf3 maintains the bone marrow cavity

et al. 2018

View full text Add to dashboard Cite

Bone marrow is the tissue filling the space between bone surfaces. Hematopoietic stem cells (HSCs) are maintained by special microenvironments known as niches within bone marrow cavities. Mesenchymal cells, termed CXC chemokine ligand 12 (CXCL12)-abundant reticular (CAR) cells or leptin receptor-positive (LepR) cells, are a major cellular component of HSC niches that gives rise to osteoblasts in bone marrow. However, it remains unclear how osteogenesis is prevented in most CAR/LepR cells to maintain HSC niches and marrow cavities. Here, using lineage tracing, we found that the transcription factor early B-cell factor 3 (Ebf3) is preferentially expressed in CAR/LepR cells and that Ebf3-expressing cells are self-renewing mesenchymal stem cells in adult marrow. When is deleted in CAR/LepR cells, HSC niche function is severely impaired, and bone marrow is osteosclerotic with increased bone in aged mice. In mice lacking and, CAR/LepR cells exhibiting a normal morphology are abundantly present, but their niche function is markedly impaired with depleted HSCs in infant marrow. Subsequently, the mutants become progressively more osteosclerotic, leading to the complete occlusion of marrow cavities in early adulthood. CAR/LepR cells differentiate into bone-producing cells with reduced HSC niche factor expression in the absence of Thus, HSC cellular niches express Ebf3 that is required to create HSC niches, to inhibit their osteoblast differentiation, and to maintain spaces for HSCs.

show abstract

Section: Car Cells Exhibiting a Normal Morphology Are Present But Hssupporting

confidence: 90%

Stem cell niche-specific Ebf3 maintains the bone marrow cavity

et al. 2018

View full text Add to dashboard Cite

show abstract

“…EBF proteins are composed of five domains; DNA binding domain (DBD), immunoglobulin‐like plexins transcription factor (IPT), atypical HLH, transactivation I domain (TSI), and transactivation II (TSII) domain and are originally discovered in rodents as a protein that regulates the differentiation of B‐lymphocyte (Crozatier, Valle, Dubois, Ibnsouda, & Vincent, ). Our previous studies in addition to others demonstrated the importance of EBF for tissue specification, differentiation, and cell movements during development of nervous, adipose, muscular, and skeletal tissues as well as feathers and bone marrow (El‐Magd, Saleh, El‐Aziz, & Salama, ; El‐Magd, Sayed‐Ahmed, Awad, & Shukry, ; Moruzzo et al, ; Seike, Omatsu, Watanabe, Kondoh, & Nagasawa, ; Tolkin & Christiaen, ; Zee et al, ).…”

Section: Introductionmentioning

confidence: 70%

“…specification, differentiation, and cell movements during development of nervous, adipose, muscular, and skeletal tissues as well as feathers and bone marrow El-Magd, Sayed-Ahmed, Awad, & Shukry, 2014;Moruzzo et al, 2017;Seike, Omatsu, Watanabe, Kondoh, & Nagasawa, 2018;Tolkin & Christiaen, 2016;Zee et al, 2013).…”

mentioning

confidence: 99%

The role of chick Ebf genes in the mediolateral patterning of the somites

El-Magd

Elsayed

El‐Shetry

et al. 2019

Genesis

View full text Add to dashboard Cite

Summary This study was conducted to check whether the three chick Early B‐cell Factor (Ebf) genes, particularly cEbf1, would be targets for Shh and Bmp signals during somites mediolateral (ML) patterning. Tissue manipulations and gain and loss of function experiments for Shh and Bmp4 were performed and the results revealed that cEbf1 expression was initiated in the cranial presomitic mesoderm by low dose of Bmp4 from the lateral mesoderm and maintained in the ventromedial part of the epithelial somite and the medial sclerotome by Shh from the notochord; while cEbf2/3 expression was induced and maintained by Bmp4 and inhibited by high dose of Shh. To determine whether Ebf1 plays a role in somite patterning, transfection of a dominant‐negative construct was carried out; this showed suppression of cPax1 expression in the medial sclerotome and upregulation and medial expansion of cEbf3 and cPax3 expression in sclerotome and dermomyotome, respectively, suggesting that Ebf1 is important for ML patterning. Thus, it is possible that low doses of Bmp4 set up Ebf1 expression which, together with Shh from the notochord, leads to establishment of the medial sclerotome and suppression of lateral identities. These data also conclude that Bmp4 is required in both the medial and lateral domain of the somitic mesoderm to keep the ML identity of the sclerotome through maintenance of cEbf gene expression. These striking findings are novel and give a new insight on the role of Bmp4 on mediolateral patterning of somites.

show abstract

“…EBF1 is a negative regulator of bone mass. ( 35,38,39 ) However, the cell types responsible for this phenotype has not been identifed, as conditional deletion of Ebf1 with Lepr‐Cre or Runx2‐cre did not alter bone properties, (38,39 ) whereas global or Prrx1‐Cre ‐mediated deletion of Ebf1 increased trabecular bone mass. ( 35,40 ) It will be important to determine if conditional inactivation of Ebf1 in PαS cells leads to improved bone properties.…”

Section: Discussionmentioning

confidence: 99%

Tmem100- and Acta2-Lineage Cells Contribute to Implant Osseointegration in a Mouse Model

Vesprey

Suh

Ayturk

et al. 2020

Journal of Bone and Mineral Research

View full text Add to dashboard Cite

Metal implants are commonly used in orthopedic surgery. The mechanical stability and longevity of implants depend on adequate bone deposition along the implant surface. The cellular and molecular mechanisms underlying peri‐implant bone formation (ie, osseointegration) are incompletely understood. Herein, our goal was to determine the specific bone marrow stromal cell populations that contribute to bone formation around metal implants. To do this, we utilized a mouse tibial implant model that is clinically representative of human joint replacement procedures. Using a lineage‐tracing approach, we found that both Acta2.creERT2 and Tmem100.creERT2 lineage cells are involved in peri‐implant bone formation, and Pdgfra‐ and Ly6a/Sca1‐expressing stromal cells (PαS cells) are highly enriched in both lineages. Single‐cell RNA‐seq analysis indicated that PαS cells are quiescent in uninjured bone tissue; however, they express markers of proliferation and osteogenic differentiation shortly after implantation surgery. Our findings indicate that PαS cells are mobilized to repair bone tissue and participate in implant osseointegration after surgery. Biologic therapies targeting PαS cells might improve osseointegration in patients undergoing orthopedic procedures. © 2021 American Society for Bone and Mineral Research (ASBMR).

show abstract

The transcription factor early B‐cell factor 1 regulates bone formation in an osteoblast‐nonautonomous manner

Cited by 12 publications

References 21 publications

Stem cell niche-specific Ebf3 maintains the bone marrow cavity

Stem cell niche-specific Ebf3 maintains the bone marrow cavity

The role of chick Ebf genes in the mediolateral patterning of the somites

Tmem100- and Acta2-Lineage Cells Contribute to Implant Osseointegration in a Mouse Model

Contact Info

Product

Resources

About