Leucine rich amelogenin peptide prevents ovariectomy-induced bone loss in mice

Amelogenins, major extra cellular matrix proteins of developing tooth enamel, are predominantly expressed by ameloblasts and play significant roles in the formation of enamel. Recently, amelogenin has been detected in various epithelial and mesenchymal tissues, implicating that it might have distinc...

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Autores principales:	Naoto Haruyama, Takayoshi Yamaza, Shigeki Suzuki, Bradford Hall, Andrew Cho, Carolyn W. Gibson, Ashok B. Kulkarni
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8e7106118c44478fa6b27d7f4126e71d
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spelling	oai:doaj.org-article:8e7106118c44478fa6b27d7f4126e71d2021-11-25T05:54:22ZLeucine rich amelogenin peptide prevents ovariectomy-induced bone loss in mice1932-6203https://doaj.org/article/8e7106118c44478fa6b27d7f4126e71d2021-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8592471/?tool=EBIhttps://doaj.org/toc/1932-6203Amelogenins, major extra cellular matrix proteins of developing tooth enamel, are predominantly expressed by ameloblasts and play significant roles in the formation of enamel. Recently, amelogenin has been detected in various epithelial and mesenchymal tissues, implicating that it might have distinct functions in various tissues. We have previously reported that leucine rich amelogenin peptide (LRAP), one of the alternate splice forms of amelogenin, regulates receptor activator of NF-kappa B ligand (RANKL) expression in cementoblast/periodontal ligament cells, suggesting that the amelogenins, especially LRAP, might function as a signaling molecule in bone metabolism. The objective of this study was to identify and define LRAP functions in bone turnover. We engineered transgenic (TgLRAP) mice using a murine 2.3kb α1(I)-collagen promoter to drive expression of a transgene consisting of LRAP, an internal ribosome entry site (IRES) and enhanced green fluorescent protein (EGFP) to study functions of LRAP in bone formation and resorption. Calvarial cell cultures from the TgLRAP mice showed increased alkaline phosphatase (ALP) activity and increased formation of mineralized nodules compared to the cells derived from wild-type (WT) mice. The TgLRAP calvarial cells also showed an inhibitory effect on osteoclastogenesis in vitro. Gene expression comparison by quantitative polymerase chain reaction (Q-PCR) in calvarial cells indicated that bone formation makers such as Runx2, Alp, and osteocalcin were increased in TgLRAP compared to the WT cells. Meanwhile, Rankl expression was decreased in the TgLRAP cells in vitro. The ovariectomized (OVX) TgLRAP mice resisted bone loss induced by ovariectomy resulting in higher bone mineral density in comparison to OVX WT mice. The quantitative analysis of calcein intakes indicated that the ovariectomy resulted in increased bone formation in both WT and TgLRAP mice; OVX TgLRAP appeared to show the most remarkably increased bone formation. The parameters for bone resorption in tissue sections showed increased number of osteoclasts in OVX WT, but not in OVX TgLRAP over that of sham operated WT or TgLRAP mice, supporting the observed bone phenotypes in OVX mice. This is the first report identifying that LRAP, one of the amelogenin splice variants, affects bone turnover in vivo.Naoto HaruyamaTakayoshi YamazaShigeki SuzukiBradford HallAndrew ChoCarolyn W. GibsonAshok B. KulkarniPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Naoto Haruyama Takayoshi Yamaza Shigeki Suzuki Bradford Hall Andrew Cho Carolyn W. Gibson Ashok B. Kulkarni Leucine rich amelogenin peptide prevents ovariectomy-induced bone loss in mice
description	Amelogenins, major extra cellular matrix proteins of developing tooth enamel, are predominantly expressed by ameloblasts and play significant roles in the formation of enamel. Recently, amelogenin has been detected in various epithelial and mesenchymal tissues, implicating that it might have distinct functions in various tissues. We have previously reported that leucine rich amelogenin peptide (LRAP), one of the alternate splice forms of amelogenin, regulates receptor activator of NF-kappa B ligand (RANKL) expression in cementoblast/periodontal ligament cells, suggesting that the amelogenins, especially LRAP, might function as a signaling molecule in bone metabolism. The objective of this study was to identify and define LRAP functions in bone turnover. We engineered transgenic (TgLRAP) mice using a murine 2.3kb α1(I)-collagen promoter to drive expression of a transgene consisting of LRAP, an internal ribosome entry site (IRES) and enhanced green fluorescent protein (EGFP) to study functions of LRAP in bone formation and resorption. Calvarial cell cultures from the TgLRAP mice showed increased alkaline phosphatase (ALP) activity and increased formation of mineralized nodules compared to the cells derived from wild-type (WT) mice. The TgLRAP calvarial cells also showed an inhibitory effect on osteoclastogenesis in vitro. Gene expression comparison by quantitative polymerase chain reaction (Q-PCR) in calvarial cells indicated that bone formation makers such as Runx2, Alp, and osteocalcin were increased in TgLRAP compared to the WT cells. Meanwhile, Rankl expression was decreased in the TgLRAP cells in vitro. The ovariectomized (OVX) TgLRAP mice resisted bone loss induced by ovariectomy resulting in higher bone mineral density in comparison to OVX WT mice. The quantitative analysis of calcein intakes indicated that the ovariectomy resulted in increased bone formation in both WT and TgLRAP mice; OVX TgLRAP appeared to show the most remarkably increased bone formation. The parameters for bone resorption in tissue sections showed increased number of osteoclasts in OVX WT, but not in OVX TgLRAP over that of sham operated WT or TgLRAP mice, supporting the observed bone phenotypes in OVX mice. This is the first report identifying that LRAP, one of the amelogenin splice variants, affects bone turnover in vivo.
format	article
author	Naoto Haruyama Takayoshi Yamaza Shigeki Suzuki Bradford Hall Andrew Cho Carolyn W. Gibson Ashok B. Kulkarni
author_facet	Naoto Haruyama Takayoshi Yamaza Shigeki Suzuki Bradford Hall Andrew Cho Carolyn W. Gibson Ashok B. Kulkarni
author_sort	Naoto Haruyama
title	Leucine rich amelogenin peptide prevents ovariectomy-induced bone loss in mice
title_short	Leucine rich amelogenin peptide prevents ovariectomy-induced bone loss in mice
title_full	Leucine rich amelogenin peptide prevents ovariectomy-induced bone loss in mice
title_fullStr	Leucine rich amelogenin peptide prevents ovariectomy-induced bone loss in mice
title_full_unstemmed	Leucine rich amelogenin peptide prevents ovariectomy-induced bone loss in mice
title_sort	leucine rich amelogenin peptide prevents ovariectomy-induced bone loss in mice
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/8e7106118c44478fa6b27d7f4126e71d
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Leucine rich amelogenin peptide prevents ovariectomy-induced bone loss in mice

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