Ameloblastin modulates osteoclastogenesis through the integrin/ERK pathway

Lu, Xuanyu; Ito, Yoshihiro; Atsawasuwan, Phimon; Dangaria, Smit; Yan, Xiulin; Wu, Tuojiang; Evans, Carla A.; Luan, Xianghong

doi:10.1016/j.bone.2013.01.041

Cited by 20 publications

(22 citation statements)

References 52 publications

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“…To prepare undecalcified ground sections, tissues were fixed in 4% paraformaldehyde, dehydrated in a graded series of ethanol, embedded in Technovit 7200 (Exakt, Oklahoma, OK, USA) and prepared into 10-mm ground sections for subsequent von Kossa staining. (26) To prepare decalcified paraffin sections, samples were demineralized in 4% EDTA. After paraffin embedding, sections were subjected to H&E staining or immunohistochemistry.…”

Section: Mouse Modelsmentioning

confidence: 99%

“…(26,27) To determine whether cytoskeletal dynamics were involved in the mechanism by which AMBN regulates gene expression, AMBN BMSCs were cultured on BSA-or AMBN-coated culture dishes for 24 hours. Cytoskeletal organization of cultured cells was visualized by F-actin staining using rhodamine-phalloidin (Fig.…”

Section: Journal Of Bone and Mineral Researchmentioning

confidence: 99%

“…The K14-driven AMBN overexpressor was based on previous studies demonstrating K14 expression in bone, (33) the successful use of this model in a previous study, (19,26) and immunohistochemistry of K14 expression in subchondral bone regions in the femur of 3-week-old mice (Fig. 6A).…”

Section: Journal Of Bone and Mineral Researchmentioning

confidence: 99%

“…(18,19) Underlining its pleiotropic nature, the AMBN molecule contains a fibronectin interaction site, heparin-binding domains, CD63-interaction domains, and calcium binding sites in both human and mouse AMBN. (20)(21)(22)(23)(24) Consistent with the multiple functions of a complex extracellular matrix molecule, recent studies have implicated AMBN in the regulation of osteogenic differentiation through Src kinase by affecting the interaction between CD63 and integrin b1, (25) in osteoclastic differentiation through the integrin/ERK pathway, (26) and in cell attachment and proliferation through RhoA and p27. (27) In calvarial bone development, AMBN reduced calvarial growth and cranial suture closure by decreasing the expression of Runx2, Osx, Ibsp, Coll, Ocn, and Opn mineralization genes through the homeobox protein Msx2.…”

mentioning

confidence: 92%

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Ameloblastin, an Extracellular Matrix Protein, Affects Long Bone Growth and Mineralization

Fukumoto

Yamada

et al. 2016

Journal of Bone and Mineral Research

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Matrix molecules such as the enamel-related calcium-binding phosphoprotein ameloblastin (AMBN) are expressed in multiple tissues, including teeth, bones, and cartilage. Here we have asked whether AMBN is of functional importance for timely long bone development and, if so, how it exerts its function related to osteogenesis. Adolescent AMBN-deficient mice (AMBN D5-6 ) suffered from a 33% to 38% reduction in femur length and an 8.4% shorter trunk spinal column when compared with WT controls, whereas there was no difference between adult animals. On a cellular level, AMBN truncation resulted in a shortened growth plate and a 41% to 49% reduction in the number of proliferating tibia chondrocytes and osteoblasts. Bone marrow stromal cells (BMSCs) isolated from AMBN mutant mice displayed defects in proliferation and differentiation potential as well as cytoskeleton organization. Osteogenesis-related growth factors, such as insulin-like growth factor 1 (IGF1) and BMP7, were also significantly (46% to 73%) reduced in AMBN-deficient BMSCs. Addition of exogenous AMBN restored cytoskeleton structures in AMBN mutant BMSCs and resulted in a dramatic 400% to 600% increase in BMP2, BMP7, and Col1A expression. Block of RhoA diminished the effect of AMBN on osteogenic growth factor and matrix protein gene expression. Addition of exogenous BMP7 and IGF1 rescued the proliferation and differentiation potential of AMBN-deficient BMSCs. Confirming the effects of AMBN on long bone growth, back-crossing of mutant mice with full-length AMBN overexpressors resulted in a complete rescue of AMBN D5-6 bone defects. Together, these data indicate that AMBN affects extracellular matrix production and cell adhesion properties in the long bone growth plate, resulting in altered cytoskeletal dynamics, increased osteogenesis-related gene expression, as well as osteoblast and chondrocyte proliferation. We propose that AMBN facilitates rapid long bone growth and an important growth spurt during the skeletogenesis of adolescent tooth-bearing vertebrates.

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Section: Mouse Modelsmentioning

confidence: 99%

Section: Journal Of Bone and Mineral Researchmentioning

confidence: 99%

Section: Journal Of Bone and Mineral Researchmentioning

confidence: 99%

mentioning

confidence: 92%

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Ameloblastin, an Extracellular Matrix Protein, Affects Long Bone Growth and Mineralization

Fukumoto

Yamada

et al. 2016

Journal of Bone and Mineral Research

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“…Sections were processed and incubated with ERP protein primary antibodies (Appendix Table 2) at a 1:50 dilution as reported (Lu et al, 2013).…”

Section: Immunohistochemistrymentioning

confidence: 99%

Expression and Function of Enamel-related Gene Products in Calvarial Development

Atsawasuwan

Ito

et al. 2013

J Dent Res

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Enamel-related gene products (ERPs) are detected in non-enamel tissues such as bone. We hypothesized that, if functional, ERP expression corresponds with distinct events during osteoblast differentiation and affects bone development and mineralization. In mouse calvariae and MC3T3 cells, expression profiles of enamel-related gene products (ERPs) correlated with key events in post-natal calvarial development and MC3T3 cell mineralization. Developing skulls from both Amel-and Ambndeficient animals were approximately 15% shorter when compared with those of wild-type controls, and their sutures remained patent for a longer period of time. Analysis of Amel-and Ambn-deficient calvariae and calvarial osteoblast cultures revealed a dramatic reduction in mineralized nodules, a significant reduction in Runx2, Sp7, Ibsp, and Msx2 expression, and a reduction in Alx4 in Amel-deficient calvariae vs. an increase in Alx4 in Ambn-deficient calvariae. Analysis of these data indicates that ERP expression follows defined developmental profiles and affects osteoblast differentiation, mineralization, and calvarial bone development. We propose that, in parallel to their role in the developing enamel matrix, ERPs have retained an evolutionary conserved function related to the biomineralization of bones.KEY WORDS: amelogenin, ameloblastin, osteoblast, calvaria, evolution, suture. A supplemental appendix to this article is published electronically only at http://jdr.sagepub.com/supplemental.

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Ameloblastin Upregulates Inflammatory Response Through Induction of IL‐1β in Human Macrophages

Otsuka

Okinaga

Ariyoshi

et al. 2017

J of Cellular Biochemistry

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Ameloblastin (AMBN) is an enamel matrix protein that has various biological functions such as healing dental pulp and repairing bone fractures. In the present study, we clarified the effect of AMBN on the expression of an inflammatory cytokine, interleukin-1β (IL-1β) in lipopolysaccharide (LPS)-treated human macrophages. Real-time RT-PCR analysis showed that LPS treatment upregulated expression of the IL-1β gene in U937 cells. Interestingly, AMBN significantly enhanced IL-1β gene expression in LPS-treated U937 cells as well as the secretion of mature IL-1β into culture supernatants by these cells. AMBN also activated caspase-1 p10 expression in LPS-treated U937 cells. Pretreatment with a caspase-1 inhibitor, Z-YVAD-FMK, downregulated the mature IL-1β expression enhanced by AMBN treatment in LPS-treated U937 cells. A co-immunoprecipitation assay showed that treatment with LPS and AMBN upregulated toll-like receptor 4 (TLR4) and myeloid differentiation primary response gene 88 (MyD88) interactions, but there was no significant difference compared with LPS treatment alone in U937 cells. In contrast, western blot analysis revealed that AMBN remarkably prolonged the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), a member of the mitogen-activated protein kinase (MAPK) family. An ERK1/2-selective inhibitor, U0126, suppressed expression of the IL-1β gene as well as its protein expression in U937 cells treated with LPS and AMBN. Taken together, these results indicate that AMBN enhances IL-1β production in LPS-treated U937 cells through ERK1/2 phosphorylation and caspase-1 activation, suggesting that AMBN upregulates the inflammatory response in human macrophages and plays an important role in innate immunity. J. Cell. Biochem. 118: 3308-3317, 2017. © 2017 Wiley Periodicals, Inc.

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Ameloblastin modulates osteoclastogenesis through the integrin/ERK pathway

Cited by 20 publications

References 52 publications

Ameloblastin, an Extracellular Matrix Protein, Affects Long Bone Growth and Mineralization

Ameloblastin, an Extracellular Matrix Protein, Affects Long Bone Growth and Mineralization

Expression and Function of Enamel-related Gene Products in Calvarial Development

Ameloblastin Upregulates Inflammatory Response Through Induction of IL‐1β in Human Macrophages

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