TGF-Beta Receptor II Is Critical for Osteogenic Progenitor Cell Proliferation and Differentiation During Postnatal Alveolar Bone Formation

Xu, Chunmei; Xie, Xudong; Zhao, Hu; Wu, Yafei; Wang, Jun; Feng, Jian Q.

doi:10.3389/fphys.2021.721775

Cited by 12 publications

(15 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In mice with conditional deletion of TGFb R2 (a major receptor for TGFb signaling) from early mesenchymal progenitor cells, alveolar bone mass and density were significantly reduced during early development and the periodontal ligament was severely damaged (Xu et al, 2021). Bone morphogenetic proteins (BMPs) belong to the TGF-b family, which is a group of highly conserved and structurally similar functional proteins.…”

Section: Tgf-b Signalingmentioning

confidence: 99%

Mechanisms of bone remodeling and therapeutic strategies in chronic apical periodontitis

Xu-tao

Wan

Liu

et al. 2022

Front. Cell. Infect. Microbiol.

View full text Add to dashboard Cite

Chronic periapical periodontitis (CAP) is a typical oral disease in which periodontal inflammation caused by an odontogenic infection eventually leads to bone loss. Uncontrolled infections often lead to extensive bone loss around the root tip, which ultimately leads to tooth loss. The main clinical issue in the treatment of periapical periodontitis is the repair of jawbone defects, and infection control is the first priority. However, the oral cavity is an open environment, and the distribution of microorganisms through the mouth in jawbone defects is inevitable. The subversion of host cell metabolism by oral microorganisms initiates disease. The presence of microorganisms stimulates a series of immune responses, which in turn stimulates bone healing. Given the above background, we intended to examine the paradoxes and connections between microorganisms and jaw defect repair in anticipation of new ideas for jaw defect repair. To this end, we reviewed the microbial factors, human signaling pathways, immune cells, and cytokines involved in the development of CAP, as well as concentrated growth factor (CGF) and stem cells in bone defect repair, with the aim of understanding the impact of microbial factors on host cell metabolism to inform the etiology and clinical management of CAP.

show abstract

Section: Tgf-b Signalingmentioning

confidence: 99%

Mechanisms of bone remodeling and therapeutic strategies in chronic apical periodontitis

Xu-tao

Wan

Liu

et al. 2022

Front. Cell. Infect. Microbiol.

View full text Add to dashboard Cite

show abstract

“…It has previously justified that TGF-β could regulate osteogenesis of periodontal ligament fibroblasts [ 30 ]. Previous study also demonstrated the essential role of TGFβR2 in osteogenic periodontal ligament cells during early alveolar bone development, and deletion of TGFβR2 in osteogenic progenitor cells resulted in significant alveolar bone loss [ 14 ]. Our results showed that miR‐223 directly binds to the 3′‐UTR of TGFβR2 mRNA, and silencing of TGFβR2 markedly inhibited PDL-derived cells osteogenesis.…”

Section: Discussionmentioning

confidence: 95%

“…It has been demonstrated to play pivotal roles in osteoblast differentiation [ 13 ]. TGFβR2, a receptor of the transforming growth factor beta (TGF-β), is also a major regulator of osteogenesis and bone repair [ 14 ]. Additionally, members of the FGFs and TGFβ families are known to be essential for osteoblast differentiation [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-223 negatively regulates the osteogenic differentiation of periodontal ligament derived cells by directly targeting growth factor receptors

et al. 2022

View full text Add to dashboard Cite

Background MicroRNA (miRNA) is accepted as a critical regulator of cell differentiation. However, whether microRNA-223 (miR-223) could affect the osteogenic differentiation of periodontal ligament (PDL)-derived cells is still unknown. The aim of this study was to explore the mechanisms underlying the roles of miR-223 in the osteogenesis of PDL-derived cells in periodontitis. Methods Microarray analysis and real-time polymerase chain reaction (RT-PCR) were used to identify difference in miR-223 expression pattern between healthy and inflamed gingival tissue. The target genes of miR-223 were predicted based on Targetscan and selected for enrichment analyses based on Metascape database. The gain-and loss-of-function experiments were performed to discuss roles of miR-223 and growth factor receptor genes in osteogenic differentiation of PDL-derived cells. The target relationship between miR-223 and growth factor receptor genes was confirmed by a dual luciferase assay. Osteogenic differentiation of PDL-derived cells was assessed by Alizarin red staining, RT-PCR and western blot detection of osteogenic markers, including osteocalcin (OCN), osteopontin (OPN) and runt-related transcription factor 2 (Runx2). Results MiR-223 was significantly increased in inflamed gingival tissues and down-regulated in PDL-derived cells during osteogenesis. The expression of miR-223 in gingival tissues was positively correlated with the clinical parameters in periodontitis patients. Overexpression of miR-223 markedly inhibited PDL-derived cells osteogenesis, which was evidenced by reduced Alizarin red staining and osteogenic markers expressions. Furthermore, two growth factor receptor genes, including fibroblast growth factor receptor 2 (FGFR2) and transforming growth factor beta receptor 2 (TGFβR2), were revealed to be direct targets of miR-223 and shown to undergo up-regulation in PDL-derived cells during osteogenesis. Moreover, suppression of FGFR2 or TGFβR2 dramatically blocked PDL-derived cells osteogenic differentiation. Conclusions Our study provides novel evidence that miR-223 can be induced by periodontitis and acts as a negative regulator of PDL-derived cells osteogenesis by targeting two growth factor receptors (TGFβR2 and FGFR2).

show abstract

“…TGFβ signaling has also been shown to drive the formation of tendon and the enthesis; loss of TGFβ signaling results in defective tendon and ligament formation [20, 21] and abnormal enthesis mineralization [49]. Furthermore, recent reports have suggested that TGFβ controls fibrocartilage and ligament cell proliferation [22, 50]. However, the molecular mechanisms by which TGFβ controls tendon and enthesis formation remain unclear.…”

Section: Discussionmentioning

confidence: 99%

“…Further studies revealed that TGFβ signaling was necessary to maintain tendon cell phenotype via Scx expression [21]. Recently, deletion of TbR2 in Gli1 expressing periodontal ligament (PDL) progenitors was shown to reduce PDL cell numbers [22]. These prior studies point to a crucial role for TGFβ in the formation of tendon and the mineralization of the tendon enthesis.…”

Section: Introductionmentioning

confidence: 99%

The role of TGFβ signaling in Gli1+ tendon and enthesis cells

Lee

Golman

Abraham

et al. 2022

Preprint

View full text Add to dashboard Cite

The development of musculoskeletal tissues such as tendon, enthesis, and bone relies on proliferation and differentiation of mesenchymal progenitor cells. Gli1+ cells have been described as putative stem cells in several tissues and are presumed to play critical roles in tissue formation and maintenance. For example, the enthesis, a fibrocartilage tissue that connects tendon to bone, is mineralized postnatally by a pool of Gli1+ progenitor cells. These cells are regulated by hedgehog signaling, but it is unclear if TGFβ signaling, necessary for tenogenesis, also plays a role in their behavior. To examine the role of TGFβ signaling in Gli1+ cell function, the receptor for TGFβ, TbR2, was deleted in Gli1-lineage cells in mice at P5. Decreased TGFβ signaling in these cells led to defects in enthesis formation by P56, including deficient bone morphometry underlying the enthesis and decreased mechanical properties. In vitro experiments using Gli1+ cells isolated from mouse tail tendons demonstrated that TGFβ controls cell differentiation and proliferation through canonical and non-canonical pathways and that TGFβ directly controls the tendon transcription factor Scx by binding to its distant enhancer. These results have implications in the development of treatments for tendon and enthesis pathologies.

show abstract

TGF-Beta Receptor II Is Critical for Osteogenic Progenitor Cell Proliferation and Differentiation During Postnatal Alveolar Bone Formation

Cited by 12 publications

References 48 publications

Mechanisms of bone remodeling and therapeutic strategies in chronic apical periodontitis

Mechanisms of bone remodeling and therapeutic strategies in chronic apical periodontitis

MicroRNA-223 negatively regulates the osteogenic differentiation of periodontal ligament derived cells by directly targeting growth factor receptors

The role of TGFβ signaling in Gli1+ tendon and enthesis cells

Contact Info

Product

Resources

About