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Article: [Pharmacological property, mechanism of action and clinical study results of Pabinafusp Alfa (Genetical Recombination) (IZCARGO

Yamamoto, Ryuji / Kawashima, Satoshi

Nihon yakurigaku zasshi. Folia pharmacologica Japonica

2022 Volume 157, Issue 1, Page(s) 62–75

Abstract: Mucopolysaccharidosis type II (MPS II) is an X-linked recessive lysosomal storage disease with the accumulation of glycosaminoglycans in tissues and organs throughout the body caused by dysfunction or loss of iduronate-2-sulfatase (IDS), resulting in ... ...

Abstract	Mucopolysaccharidosis type II (MPS II) is an X-linked recessive lysosomal storage disease with the accumulation of glycosaminoglycans in tissues and organs throughout the body caused by dysfunction or loss of iduronate-2-sulfatase (IDS), resulting in somatic and central nervous system (CNS) disorders. Although enzyme replacement therapy (ERT) with recombinant human IDS is the current first-line therapy for MPS II, it is not effective for the CNS because intravenously administered enzyme cannot cross the blood-brain barrier (BBB) and thereby does not reach the brain parenchyma. Pabinafusp alfa, approved in March 2021 in Japan, is a recombinant fusion protein composed of human IDS and humanized anti-human transferrin receptor (hTfR) antibody, utilizing the BBB-penetrating technology "J-Brain Cargo
MeSH term(s)	Animals ; Disease Models, Animal ; Enzyme Replacement Therapy ; Humans ; Iduronate Sulfatase/genetics ; Iduronate Sulfatase/therapeutic use ; Mice ; Mucopolysaccharidosis II/drug therapy ; Mucopolysaccharidosis II/genetics ; Recombination, Genetic
Chemical Substances	Iduronate Sulfatase (EC 3.1.6.13)
Language	Japanese
Publishing date	2022-01-01
Publishing country	Japan
Document type	Journal Article
ZDB-ID	1097532-9
ISSN	1347-8397 ; 0015-5691
ISSN (online)	1347-8397
ISSN	0015-5691
DOI	10.1254/fpj.21080
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Article ; Online: Hyaluronan and chondroitin sulfate in chicken-vegetable bone broth delay osteoporosis progression.

Seki, Yuka / Ohkuma, Risako Chiba / Miyakawa, Yuri / Karakida, Takeo / Yamamoto, Ryuji / Yamakoshi, Yasuo

Journal of food science

2024 Volume 89, Issue 3, Page(s) 1791–1803

Abstract: Bone broth has recently gained worldwide recognition as a superfood that supplements several nutrients lacking in modern human diets; however, little is known of its efficacy on osteoporosis. Therefore, we aimed to identify the components of chicken- ... ...

Abstract	Bone broth has recently gained worldwide recognition as a superfood that supplements several nutrients lacking in modern human diets; however, little is known of its efficacy on osteoporosis. Therefore, we aimed to identify the components of chicken-vegetable bone broth (CVBB) that are associated with osteoporosis prevention and verified the efficacy of these components using in vivo studies. In biochemical and cell biological experiments, CVBB was fractionated using ion exchange chromatography (IEC), and the effect of each IEC fraction on osteoclast differentiation was evaluated based on tartrate-resistant acid phosphatase (TRAP) activity, TRAP staining, and quantitative polymerase chain reaction analysis using mouse macrophage-like cells (RAW264 cell). In animal experiments, an ovariectomized (OVX) rat model was generated, followed by whole bone broth (OVX/CVBB) or IEC fraction (OVX/CVBB-Ext) administration and bone structural parameter characterization of OVX rat tibia based on micro-CT. Four CVBB fractions were obtained using IEC, and the fraction containing both hyaluronan and chondroitin sulfate (CVBB-Ext) led to the maximum inhibition of RAW264 cell differentiation. CVBB-Ext downregulated the expression of osteoclast differentiation marker genes. In animal experiments, the OVX group showed a clear decrease in bone density compared to that in the Sham operation group. The OVX/CVBB and OVX/CVBB-Ext groups showed increased bone mineral density and bone volume/tissue volume values compared to those in the OVX/control group. These results suggested that CVBB and CVBB-Ext slowed osteoporosis progression. Therefore, we conclude that hyaluronan and chondroitin sulfate in CVBB are key substances that impede osteoporosis progression. PRACTICAL APPLICATION: This study provides practical information on the effects of bone broth ingredients on osteoporosis to expand the current knowledge on the efficacy of bone broth, which is a widely consumed food. These results may help in the future development of bone broth as a dietary supplement for managing osteoporosis.
MeSH term(s)	Mice ; Humans ; Rats ; Animals ; Vegetables ; Chondroitin Sulfates/pharmacology ; Hyaluronic Acid/pharmacology ; Chickens ; Osteoporosis/metabolism ; Bone Density
Chemical Substances	Chondroitin Sulfates (9007-28-7) ; Hyaluronic Acid (9004-61-9)
Language	English
Publishing date	2024-02-05
Publishing country	United States
Document type	Journal Article
ZDB-ID	241615-3
ISSN	1750-3841 ; 0022-1147
ISSN (online)	1750-3841
ISSN	0022-1147
DOI	10.1111/1750-3841.16962
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Article: Dose-dependent effects of a brain-penetrating iduronate-2-sulfatase on neurobehavioral impairments in mucopolysaccharidosis II mice.

Morimoto, Hideto / Morioka, Hiroki / Imakiire, Atsushi / Yamamoto, Ryuji / Hirato, Tohru / Sonoda, Hiroyuki / Minami, Kohtaro

Molecular therapy. Methods & clinical development

2022 Volume 25, Page(s) 534–544

Abstract: Deposition of heparan sulfate (HS) in the brain of patients with mucopolysaccharidosis II (MPS II) is believed to be the leading cause of neurodegeneration, resulting in several neurological signs and symptoms, including neurocognitive impairment. We ... ...

Abstract	Deposition of heparan sulfate (HS) in the brain of patients with mucopolysaccharidosis II (MPS II) is believed to be the leading cause of neurodegeneration, resulting in several neurological signs and symptoms, including neurocognitive impairment. We recently showed that pabinafusp alfa, a blood-brain-barrier-penetrating fusion protein consisting of iduronate-2-sulfatase and anti-human transferrin receptor antibody, stabilized learning ability by preventing the deposition of HS in the CNS of MPS II mice. We further examined the dose-dependent effect of pabinafusp alfa on neurological function in relation to its HS-reducing efficacy in a mouse model of MPS II. Long-term intravenous treatment with low (0.1 mg/kg), middle (0.5 mg/kg), and high (2.0 mg/kg) doses of the drug dose-dependently decreased HS concentration in the brain and cerebrospinal fluid (CSF). A comparable dose-dependent effect in the prevention of neuronal damage in the CNS, and dose-dependent improvements in neurobehavioral performance tests, such as gait analysis, pole test, Y maze, and Morris water maze, were also observed. Notably, the water maze test performance was inversely correlated with the HS levels in the brain and CSF. This study provides nonclinical evidence substantiating a quantitative dose-dependent relationship between HS reduction in the CNS and neurological improvements in MPS II.
Language	English
Publishing date	2022-05-10
Publishing country	United States
Document type	Journal Article
ZDB-ID	2872938-9
ISSN	2329-0501 ; 2329-0501
ISSN (online)	2329-0501
ISSN	2329-0501
DOI	10.1016/j.omtm.2022.05.002
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Article ; Online: Synergistic effect of FGF-2 and TGF-β1 on the mineralization of human umbilical cord perivascular cells.

Yabe, Masahiro / Karakida, Takeo / Onuma, Kazuo / Yamamoto, Ryuji / Chiba-Ohkuma, Risako / Asada, Sakurako / Yamakoshi, Yasuo / Gomi, Kazuhiro

Archives of oral biology

2023 Volume 156, Page(s) 105826

Abstract: Objective: Human umbilical cord perivascular cells (HUCPVCs) are derived from the human umbilical cord perivascular tissue and are expected to replace mesenchymal stromal cells in the future. We investigated the synergistic effects of fibroblast growth ... ...

Abstract	Objective: Human umbilical cord perivascular cells (HUCPVCs) are derived from the human umbilical cord perivascular tissue and are expected to replace mesenchymal stromal cells in the future. We investigated the synergistic effects of fibroblast growth factor 2 (FGF-2) and transforming growth factor-beta 1 (TGF-β1) on HUCPVC mineralization. Design: We prepared HUCPVCs with (FGF(+)HUCPVCs) or without FGF-2 (FGF(-)HUCPVCs) in the presence of activated vitamin D Results: FGF(+)HUCPVCs exhibited higher intracellular alkaline phosphatase (ALP) gene expression and ALP activity, and their cell proliferation rate was higher than that of FGF(-)HUCPVCs. The expression levels of osteoblast marker genes increased in FGF(+)HUCPVCs, whereas those of elastic fiber and muscle cell markers increased in FGF(-)HUCPVCs. The expression of genes related to matrix vesicle-mediated mineralization was increased in FGF(+)HUCPVCs. While FGF(-)HUCPVCs displayed myofibroblast-like properties and could not induce mineralization, FGF(+)HUCPVCs demonstrated the ability to produce mineralized nodules. The resulting mineralized nodules consisted of hydroxyapatite as the major phase and minor amounts of octacalcium phosphate. The mineralized nodules exhibited the morphological characteristics of bone hydroxyapatite, composed of fibrous hydroxyapatite nanorods and polycrystalline sheets. Conclusion: We found that FGF-2 synergizes with TGF-β1 and is a key factor in the differentiation of HUCPVCs into osteoblast-like cells. Thus, HUCPVCs can potentially serve as a new stem cell source for future bone regeneration and dental treatments.
MeSH term(s)	Humans ; Fibroblast Growth Factor 2/pharmacology ; Transforming Growth Factor beta1/pharmacology ; Transforming Growth Factor beta1/metabolism ; Cell Differentiation ; Mesenchymal Stem Cells ; Umbilical Cord ; Hydroxyapatites/pharmacology
Chemical Substances	Fibroblast Growth Factor 2 (103107-01-3) ; Transforming Growth Factor beta1 ; Hydroxyapatites
Language	English
Publishing date	2023-10-19
Publishing country	England
Document type	Journal Article
ZDB-ID	80227-x
ISSN	1879-1506 ; 0003-9969
ISSN (online)	1879-1506
ISSN	0003-9969
DOI	10.1016/j.archoralbio.2023.105826
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Article ; Online: New insights into bioactivity of ceria-stabilized zirconia: Direct bonding to bone-like hydroxyapatite at nanoscale.

Saito, Mari M / Onuma, Kazuo / Yamamoto, Ryuji / Yamakoshi, Yasuo

Materials science & engineering. C, Materials for biological applications

2020 Volume 121, Page(s) 111665

Abstract: Osseointegration resulting from biomineralization means tight bone-implant attachment, which is clinically essential for successful dental implant treatment. The osseointegration ability of ceria-stabilized zirconia, a promising implant material, has ... ...

Abstract	Osseointegration resulting from biomineralization means tight bone-implant attachment, which is clinically essential for successful dental implant treatment. The osseointegration ability of ceria-stabilized zirconia, a promising implant material, has been questionable and is unclear despite its clinical use due to zirconia's bioinert nature. The purpose of this research was to investigate the osseointegration ability of ceria-stabilized zirconia by clarifying its bioactivity. Here we show that ceria-stabilized zirconia is highly bioactive, contrary to the general consensus. Transmission electron microscopy observation revealed that the zirconia nanocrystals of a ceria-stabilized zirconia substrate directly bonded to osteoblastic cell-precipitated hydroxyapatite crystals at lattice fringe scale. This bonding was achieved without chemical treatment of the substrate surface before use. Hydroxyapatite crystals exhibited a morphology of flexible nanofibers less than 10 nm wide with nanometer-thick plates filling the spaces between nanofibers. Elemental analysis of the hydroxyapatites showed that they contained alkaline metal cations (Na, Mg, and K) as minor elements and that their average Ca/P atomic % ratio was ~1.40, similar to those of bone apatite. High bioactivity of ceria-stabilized zirconia resulted in direct bonding to bone-like hydroxyapatite, suggesting nanoscale direct osseointegration with bone in vivo that contributes to improving the success rate of dental implant treatment.
MeSH term(s)	Dental Implants ; Durapatite ; Hydroxyapatites ; Osseointegration ; Surface Properties ; Titanium ; Zirconium
Chemical Substances	Dental Implants ; Hydroxyapatites ; Durapatite (91D9GV0Z28) ; Zirconium (C6V6S92N3C) ; Titanium (D1JT611TNE) ; zirconium oxide (S38N85C5G0)
Language	English
Publishing date	2020-10-22
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2012160-X
ISSN	1873-0191 ; 0928-4931
ISSN (online)	1873-0191
ISSN	0928-4931
DOI	10.1016/j.msec.2020.111665
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Article ; Online: Dentin sialophosphoprotein-derived proteins in porcine pulp and dentin - Gene expression and function.

Yamamoto, Ryuji / Yamakoshi, Yasuo

Journal of oral biosciences

2016 Volume 58, Issue 4, Page(s) 120–127

Abstract: Background: Dentin sialophosphoprotein (DSPP) is the most abundant non-collagenous protein in dentin and is critical for the proper mineralization of tooth dentin. DSPP is processed by proteases into three major domains: dentin sialoprotein (DSP), ... ...

Abstract	Background: Dentin sialophosphoprotein (DSPP) is the most abundant non-collagenous protein in dentin and is critical for the proper mineralization of tooth dentin. DSPP is processed by proteases into three major domains: dentin sialoprotein (DSP), dentin glycoprotein (DGP) and dentin phosphoprotein (DPP). Two mRNA variants are expressed from the Dspp gene. The larger transcript encodes full-length DSPP (DSP+DGP+DPP). The shorter transcript encodes only DSP. Highlight: We fractionated DSPP-derived proteins from the dental pulp of developing porcine incisors using heparin chromatography. DSP was identified, but little DPP could be detected in any fraction. Expression of full-length Dspp mRNA, determined by qPCR analysis, was significantly higher in odontoblasts than in pulp. Expression of DSP-only mRNA was almost equal in odontoblasts and in the body of pulp. Expression of full-length Dspp mRNA was also significantly higher than expression of DSP-only mRNA in odontoblasts. Both the full-length and DSP-only Dspp mRNA showed only trace expression in the pulp tip. We purified TGF-β1-unbound or -bound to DPP and DSP using high performance liquid chromatography (HPLC) and measured its alkaline phosphatase stimulating activity in human periodontal cells with or without TGF-β receptor inhibitor. We also incubated carrier-free human recombinant TGF-β1 (CF-hTGF-β1) protein with TGF-β1-unbound DPP or DSP and characterized binding ability. Conclusion: DSP-only is expressed throughout odontoblast differentiation, while full-length DSPP is predominantly expressed by odontoblasts only after they have differentiated from mesenchymal cells. DPP and DSP rescued the loss of TGF-β1 activity. Type I collagen was infrequently bound to CF-hTGF-β1.
Language	English
Publishing date	2016-07-07
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	2218267-6
ISSN	1880-3865 ; 1349-0079
ISSN (online)	1880-3865
ISSN	1349-0079
DOI	10.1016/j.job.2016.06.001
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Article: Nonclinical safety evaluation of pabinafusp alfa, an anti-human transferrin receptor antibody and iduronate-2-sulfatase fusion protein, for the treatment of neuronopathic mucopolysaccharidosis type II.

Yamamoto, Ryuji / Yoden, Eiji / Tanaka, Noboru / Kinoshita, Masafumi / Imakiire, Atsushi / Hirato, Tohru / Minami, Kohtaro

Molecular genetics and metabolism reports

2021 Volume 27, Page(s) 100758

Abstract: Pabinafusp alfa is a fusion protein comprising a humanized anti-human transferrin receptor (TfR) antibody and human iduronate-2-sulfatase. It was developed as a novel modality to target central nervous system-related symptoms observed in patients with ... ...

Abstract	Pabinafusp alfa is a fusion protein comprising a humanized anti-human transferrin receptor (TfR) antibody and human iduronate-2-sulfatase. It was developed as a novel modality to target central nervous system-related symptoms observed in patients with mucopolysaccharidosis type II (MPS II, also known as Hunter syndrome). As the fusion protein contains an entire IgG1 molecule that binds TfR, there may be specific safety concerns, such as unexpected cellular toxicity due to its effector functions or its ability to inhibit iron metabolism, in addition to general safety concerns. Here, we present the comprehensive results of a nonclinical safety assessment of pabinafusp alfa. Pabinafusp alfa did not exhibit effector functions, as assessed by antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity studies in TfR-expressing hematopoietic cells. Repeat-dose toxicity studies in cynomolgus monkeys showed that pabinafusp alfa did not induce any significant toxicological changes at doses up to 30 mg/kg/week upon intravenous administration for up to 26 weeks. Interaction of transferrin with TfR was not inhibited by pabinafusp alfa, suggesting that the effect of pabinafusp alfa on the physiological iron transport system is minimal, which was confirmed by toxicity studies in cynomolgus monkeys. These findings suggest that pabinafusp alfa is expected to be safe for long-term use in individuals with MPS II.
Language	English
Publishing date	2021-04-18
Publishing country	United States
Document type	Journal Article
ZDB-ID	2821908-9
ISSN	2214-4269
ISSN	2214-4269
DOI	10.1016/j.ymgmr.2021.100758
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Article ; Online: Pathogenic Roles of Heparan Sulfate and Its Use as a Biomarker in Mucopolysaccharidoses.

Minami, Kohtaro / Morimoto, Hideto / Morioka, Hiroki / Imakiire, Atsushi / Kinoshita, Masafumi / Yamamoto, Ryuji / Hirato, Tohru / Sonoda, Hiroyuki

International journal of molecular sciences

2022 Volume 23, Issue 19

Abstract: Heparan sulfate (HS) is an essential glycosaminoglycan (GAG) as a component of proteoglycans, which are present on the cell surface and in the extracellular matrix. HS-containing proteoglycans not only function as structural constituents of the basal ... ...

Abstract	Heparan sulfate (HS) is an essential glycosaminoglycan (GAG) as a component of proteoglycans, which are present on the cell surface and in the extracellular matrix. HS-containing proteoglycans not only function as structural constituents of the basal lamina but also play versatile roles in various physiological processes, including cell signaling and organ development. Thus, inherited mutations of genes associated with the biosynthesis or degradation of HS can cause various diseases, particularly those involving the bones and central nervous system (CNS). Mucopolysaccharidoses (MPSs) are a group of lysosomal storage disorders involving GAG accumulation throughout the body caused by a deficiency of GAG-degrading enzymes. GAGs are stored differently in different types of MPSs. Particularly, HS deposition is observed in patients with MPS types I, II, III, and VII, all which involve progressive neuropathy with multiple CNS system symptoms. While therapies are available for certain symptoms in some types of MPSs, significant unmet medical needs remain, such as neurocognitive impairment. This review presents recent knowledge on the pathophysiological roles of HS focusing on the pathogenesis of MPSs. We also discuss the possible use and significance of HS as a biomarker for disease severity and therapeutic response in MPSs.
MeSH term(s)	Biomarkers ; Glycosaminoglycans ; Heparan Sulfate Proteoglycans ; Heparitin Sulfate/metabolism ; Humans ; Mucopolysaccharidoses/pathology ; Mucopolysaccharidosis I
Chemical Substances	Biomarkers ; Glycosaminoglycans ; Heparan Sulfate Proteoglycans ; Heparitin Sulfate (9050-30-0)
Language	English
Publishing date	2022-10-03
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms231911724
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Article ; Online: Characterization of bioactive substances involved in the induction of bone augmentation using demineralized bone sheets.

Saito, Haruka / Chiba-Ohkuma, Risako / Yamakoshi, Yasuo / Karakida, Takeo / Yamamoto, Ryuji / Shirai, Mai / Ohkubo, Chikahiro

International journal of implant dentistry

2022 Volume 8, Issue 1, Page(s) 49

Abstract: Purpose: To investigate the bone augmentation ability of demineralized bone sheets mixed with allogeneic bone with protein fractions containing bioactive substances and the interaction between coexisting bioactive substances and proteins.: Methods: ... ...

Abstract	Purpose: To investigate the bone augmentation ability of demineralized bone sheets mixed with allogeneic bone with protein fractions containing bioactive substances and the interaction between coexisting bioactive substances and proteins. Methods: Four types of demineralized bone sheets mixed with allogeneic bone in the presence or absence of bone proteins were created. Transplantation experiments using each demineralized bone sheet were performed in rats, and their ability to induce bone augmentation was analysed by microcomputed tomography images. Bioactive substances in bone proteins were isolated by heparin affinity chromatography and detected by the measurement of alkaline phosphatase activity in human periodontal ligament cells and dual luciferase assays. Noncollagenous proteins (NCPs) coexisting with the bioactive substances were identified by mass spectrometry, and their interaction with bioactive substances was investigated by in vitro binding experiments. Results: Demineralized bone sheets containing bone proteins possessed the ability to induce bone augmentation. Bone proteins were isolated into five fractions by heparin affinity chromatography, and transforming growth factor-beta (TGF-β) was detected in the third fraction (Hep-c). Dentin matrix protein 1 (DMP1), matrix extracellular phosphoglycoprotein (MEPE), and biglycan (BGN) also coexisted in Hep-c, and the binding of these proteins to TGF-β increased TGF-β activity by approximately 14.7% to 32.7%. Conclusions: Demineralized bone sheets are capable of inducing bone augmentation, and this ability is mainly due to TGF-β in the bone protein mixed with the sheets. The activity of TGF-β is maintained when binding to bone NCPs such as DMP1, MEPE, and BGN in the sheets.
MeSH term(s)	Rats ; Humans ; Animals ; X-Ray Microtomography ; Transforming Growth Factor beta/metabolism ; Periodontal Ligament/metabolism ; Heparin
Chemical Substances	Transforming Growth Factor beta ; Heparin (9005-49-6)
Language	English
Publishing date	2022-11-01
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2198-4034
ISSN (online)	2198-4034
DOI	10.1186/s40729-022-00449-9
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Article ; Online: Response of TGF-β isoforms in epithelial-mesenchymal transition of enamel epithelial cells.

Miyakawa, Yuri / Chiba-Ohkuma, Risako / Karakida, Takeo / Yamamoto, Ryuji / Kobayashi, Saeko / Yamakoshi, Yasuo / Asada, Yoshinobu

Archives of oral biology

2022 Volume 143, Page(s) 105540

Abstract: Objective: During enamel formation, transforming growth factor-beta (TGF-β) isoforms exhibit different activities for gene expression, apoptosis, and endocytosis. This study aimed to investigate the differential response of TGF-β isoforms to epithelial- ... ...

Abstract	Objective: During enamel formation, transforming growth factor-beta (TGF-β) isoforms exhibit different activities for gene expression, apoptosis, and endocytosis. This study aimed to investigate the differential response of TGF-β isoforms to epithelial-mesenchymal transition (EMT) in enamel epithelial cells. Design: Using a mouse enamel epithelial cell line (mHAT9d) cultured in the presence of each TGF-β isoform, (1) the morphological changes in EMT were explored, (2) EMT-related genes were analyzed by next-generation sequencing (NGS), (3) TGF-β pathway for EMT was identified by inhibition experiments, and (4) the expression of the TGF-β receptor gene in response to the binding affinity of the TGF-β isoform were analyzed. Results: EMT was observed in mHAT9d cultured in the presence of TGF-β1 and β3 but not TGF-β2. The expression of both epithelial and mesenchymal marker genes was observed in mHAT9d exhibiting EMT. NGS analysis suggested extracellular signal-regulated kinase (ERK) and Rho pathways as TGF-β signaling pathways associated with EMT. However, EMT in mHAT9d cultured in the presence of TGF-β1 or β3 occurred even in presence of an ERK1/2 inhibitor and was suppressed by Rho-kinase inhibitor. The expression of co-receptors for TGF-β signaling in mHAT9d cells reduced following stimulation with each TGF-β isoform. In contrast, endoglin levels increased following TGF-β1 or β3 stimulation, but no change was noted in response to TGF-β2. Conclusions: We propose that in TGF-β-stimulated enamel epithelial cells, EMT mainly occurred via the Rho signaling pathway, and the differences in response across TGF-β isoforms were due to their endoglin-mediated binding affinity for the TGF-β receptor.
MeSH term(s)	Dental Enamel/metabolism ; Endoglin/metabolism ; Epithelial Cells/metabolism ; Epithelial-Mesenchymal Transition ; Extracellular Signal-Regulated MAP Kinases/metabolism ; Protein Isoforms/metabolism ; Receptors, Transforming Growth Factor beta/metabolism ; Transforming Growth Factor beta1/metabolism ; Transforming Growth Factor beta1/pharmacology ; Transforming Growth Factors/metabolism ; rho-Associated Kinases/metabolism
Chemical Substances	Endoglin ; Protein Isoforms ; Receptors, Transforming Growth Factor beta ; Transforming Growth Factor beta1 ; Transforming Growth Factors (76057-06-2) ; rho-Associated Kinases (EC 2.7.11.1) ; Extracellular Signal-Regulated MAP Kinases (EC 2.7.11.24)
Language	English
Publishing date	2022-09-06
Publishing country	England
Document type	Journal Article
ZDB-ID	80227-x
ISSN	1879-1506 ; 0003-9969
ISSN (online)	1879-1506
ISSN	0003-9969
DOI	10.1016/j.archoralbio.2022.105540
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