ACVR1 is essential for periodontium development and promotes alveolar bone formation

Zhang, Xue; Liu, Qilin; Zhao, Huan; Hu, Yue; Liu, Cangwei; Yan, Guangxing; Li, Daowei; Mishina, Yuji; Shi, Ce; Sun, Hongchen

doi:10.1016/j.archoralbio.2018.07.019

Cited by 4 publications

(8 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Osterix-Cre mice, causes an increased osteoclast formation and alveolar bone with higher porosity (Zhang et al, 2018). Together, the current study and the study by Zhang et al suggest a modulatory role of ACVR1 in osteoclast formation.…”

supporting

confidence: 82%

“…Considering the role of ACVR1 in osteoclastogenesis, the current study shows that activation of the receptor leads to less osteoclasts. Interestingly, deletion of the receptor, such as done in Osterix‐Cre mice, causes an increased osteoclast formation and alveolar bone with higher porosity (Zhang et al, ). Together, the current study and the study by Zhang et al suggest a modulatory role of ACVR1 in osteoclast formation.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

The effect of Activin‐A on periodontal ligament fibroblasts‐mediated osteoclast formation in healthy donors and in patients with fibrodysplasia ossificans progressiva

Schoenmaker

Wouters

Micha

et al. 2018

Journal Cellular Physiology

View full text Add to dashboard Cite

Fibrodysplasia ossificans progressiva (FOP) is a genetic disease characterized by heterotopic ossification (HO). The disease is caused by a mutation in the activin receptor type 1 ( ACVR1 ) gene that enhances this receptor's responsiveness to Activin‐A. Binding of Activin‐A to the mutated ACVR1 receptor induces osteogenic differentiation. Whether Activin‐A also affects osteoclast formation in FOP is not known. Therefore we investigated its effect on the osteoclastogenesis‐inducing potential of periodontal ligament fibroblasts (PLF) from teeth of healthy controls and patients with FOP. We used western blot analysis of phosphorylated SMAD3 (pSMAD3) and quantitative polymerase chain reaction to assess the effect of Activin‐A on the PLF. PLF‐induced osteoclast formation and gene expression were studied by coculturing control and FOP PLF with CD14‐positive osteoclast precursor cells from healthy donors. Osteoclast formation was also assessed in control CD14 cultures stimulated by macrophage colony‐stimulating factor (M‐CSF) and receptor activator of nuclear factor kappa‐B ligand (RANK‐L). Although Activin‐A increased activation of the pSMAD3 pathway in both control and FOP PLF, it increased ACVR1, FK binding protein 12 (FKBP12), an inhibitor of DNA binding 1 protein (ID‐1) expression only in FOP PLF. Activin‐A inhibited PLF mediated osteoclast formation albeit only significantly when induced by FOP PLF. In these cocultures, it reduced M‐CSF and dendritic cell‐specific transmembrane protein (DC‐STAMP) expression. Activin‐A also inhibited osteoclast formation in M‐CSF and RANK‐L mediated monocultures of CD14+ cells by inhibiting their proliferation. This study brings new insight on the role of Activin A in osteoclast formation, which may further add to understanding FOP pathophysiology; in addition to the known Activin‐A‐mediated HO, this study shows that Activin‐A may also inhibit osteoclast formation, thereby further promoting HO formation.

show abstract

supporting

confidence: 82%

Section: Discussionmentioning

confidence: 99%

The effect of Activin‐A on periodontal ligament fibroblasts‐mediated osteoclast formation in healthy donors and in patients with fibrodysplasia ossificans progressiva

Schoenmaker

Wouters

Micha

et al. 2018

Journal Cellular Physiology

View full text Add to dashboard Cite

show abstract

“…Our current finding that ACVR1 positively regulated mandibular bone mass is supported by our previous study, demonstrating that ACVR1 is responsible for alveolar bone mass in the periodontium (X. Zhang et al, 2018). Moreover, our results also highlighted that ACVR1 played different roles in terms of bone mass among bones in different anatomical sites.…”

Section: Discussionsupporting

confidence: 88%

“…Our results and other studies showed that BMP signaling mediated by BMP receptor in osteoblast lineage cells promoted osteoblast differentiation (Kamiya et al, 2010;Kamiya et al, 2011;Kamiya, Ye, Kobayashi, Lucas, et al, 2008;Lim et al, 2016;Mishina et al, 2004;Shi et al, 2018;X. Zhang et al, 2018).…”

Section: Discussionsupporting

confidence: 81%

Acvr1 deletion in osteoblasts impaired mandibular bone mass through compromised osteoblast differentiation and enhanced sRANKL‐induced osteoclastogenesis

Hao

Liu

et al. 2020

Journal Cellular Physiology

Self Cite

View full text Add to dashboard Cite

Bone morphogenetic protein (BMP) signaling is well known in bone homeostasis. However, the physiological effects of BMP signaling on mandibles are largely unknown, as the mandible has distinct functions and characteristics from other bones. In this study, we investigated the roles of BMP signaling in bone homeostasis of the mandibles by deleting BMP type I receptor Acvr1 in osteoblast lineage cells with Osterix-Cre. We found mandibular bone loss in conditional knockout mice at the ages of postnatal day 21 and 42 in an age-dependent manner. The decreased bone mass was related to compromised osteoblast differentiation together with enhanced osteoclastogenesis, which was secondary to the changes in osteoblasts in vivo. In vitro study revealed that deletion of Acvr1 in the mandibular bone marrow stromal cells (BMSCs) significantly compromised osteoblast differentiation. When wild type bone marrow macrophages were cocultured with BMSCs lacking Acvr1 both directly and indirectly, both proliferation and differentiation of osteoclasts were induced as evidenced by an increase of multinucleated cells, compared with cocultured with control BMSCs. Furthermore, we demonstrated that the increased osteoclastogenesis in vitro was at least partially due to the secretion of soluble receptor activator of nuclear factor-κB ligand (sRANKL), which is probably the reason for the mandibular bone loss in vivo. Overall, our results proposed that ACVR1 played essential roles in maintaining mandibular bone homeostasis through osteoblast differentiation and osteoblast-osteoclast communication via sRANKL.

show abstract

“…Yet, certain differences were observed regarding the age of induced deletion, and further studies are required to elucidate the functional mechanisms in relation to BMP receptors and bone regulation [84,85]. Furthermore, ACVR1 is required for periodontium ligament and alveolar bone development, regulation, and remodelling [86]. Loss of Acvr1 in the dental mesenchyme promoted dental defects.…”

Section: Bone Regulation and Skeletal Developmentmentioning

confidence: 99%

ACVR1 Function in Health and Disease

Valer

Sánchez-de-Diego

Pimenta-Lopes

et al. 2019

Cells

View full text Add to dashboard Cite

Activin A receptor type I (ACVR1) encodes for a bone morphogenetic protein type I receptor of the TGFβ receptor superfamily. It is involved in a wide variety of biological processes, including bone, heart, cartilage, nervous, and reproductive system development and regulation. Moreover, ACVR1 has been extensively studied for its causal role in fibrodysplasia ossificans progressiva (FOP), a rare genetic disorder characterised by progressive heterotopic ossification. ACVR1 is linked to different pathologies, including cardiac malformations and alterations in the reproductive system. More recently, ACVR1 has been experimentally validated as a cancer driver gene in diffuse intrinsic pontine glioma (DIPG), a malignant childhood brainstem glioma, and its function is being studied in other cancer types. Here, we review ACVR1 receptor function and signalling in physiological and pathological processes and its regulation according to cell type and mutational status. Learning from different functions and alterations linked to ACVR1 is a key step in the development of interdisciplinary research towards the identification of novel treatments for these pathologies.

show abstract

ACVR1 is essential for periodontium development and promotes alveolar bone formation

Cited by 4 publications

References 29 publications

The effect of Activin‐A on periodontal ligament fibroblasts‐mediated osteoclast formation in healthy donors and in patients with fibrodysplasia ossificans progressiva

The effect of Activin‐A on periodontal ligament fibroblasts‐mediated osteoclast formation in healthy donors and in patients with fibrodysplasia ossificans progressiva

Acvr1 deletion in osteoblasts impaired mandibular bone mass through compromised osteoblast differentiation and enhanced sRANKL‐induced osteoclastogenesis

ACVR1 Function in Health and Disease

Contact Info

Product

Resources

About