Bone Lining Cells Could Be Sources of Bone Marrow Adipocytes

BackgroundRecently, lineage-tracing studies demonstrated that parathyroid hormone and anti-sclerostin antibody (Scl-Ab) can convert bone lining cells (BLCs) into active osteoblasts. However, BLCs might also be differentiated into other lineages. Here we investigated whether BLCs could differentiate...

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Autores principales:	Ji Yeon Lee, Jae-Yeon Yang, Sang Wan Kim
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	bone marrow adipocyte bone lining cell anti-sclerostin antibody rosiglitazone osteoblast Diseases of the endocrine glands. Clinical endocrinology RC648-665
Acceso en línea:	https://doaj.org/article/0a84f972ec5e4da1b35d35b14a99ce09
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spelling	oai:doaj.org-article:0a84f972ec5e4da1b35d35b14a99ce092021-12-03T09:34:32ZBone Lining Cells Could Be Sources of Bone Marrow Adipocytes1664-239210.3389/fendo.2021.766254https://doaj.org/article/0a84f972ec5e4da1b35d35b14a99ce092021-12-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fendo.2021.766254/fullhttps://doaj.org/toc/1664-2392BackgroundRecently, lineage-tracing studies demonstrated that parathyroid hormone and anti-sclerostin antibody (Scl-Ab) can convert bone lining cells (BLCs) into active osteoblasts. However, BLCs might also be differentiated into other lineages. Here we investigated whether BLCs could differentiate into bone marrow adipocytes (BMAds) and whether Scl-Ab could suppress this process.MethodsDmp1-CreERt2:mTmG mice were injected with 0.5 mg of 4-hydroxytamoxifen once weekly from postnatal week 4 to week 8. The mice were treated with either vehicle or rosiglitazone for 8 weeks (weeks 12–20). Moreover, they were administered either vehicle or Scl-Ab (50 mg/kg) twice weekly for 4 weeks (weeks 16–20, N = 4–6/group). We chased the GFP+ cells from the endosteal surface to the bone marrow (BM) of the femur. Using immunohistochemical staining, the numbers of perilipin+ or GFP+/perilipin double+ cells in the BM were quantified. In addition, serum N-terminal propeptide of type I procollagen (P1NP) levels were measured at each time point, and bone mass was analyzed at 20 weeks using micro-computed tomography.ResultsScl-Ab administration significantly reversed the decreases in bone parameters induced by rosiglitazone. Plump GFP+ cells, presumably active osteoblasts, and extremely flat GFP+ cells, presumably BLCs, were present on the endosteal surface of the femur at 8 and 12 weeks, respectively, in line with prior findings. When we chased the GFP+ cells, rosiglitazone significantly increased the number of GFP/perilipin double+ BMAds compared to the effects of the vehicle (P < 0.001), and overlapping Scl-Ab administration decreased the number of GFP/perilipin double + BMAd compared to rosiglitazone alone (P < 0.001). In addition, we found that osteoblast lineage cells such as BLCs might express PPARγ on immunohistochemical staining. When rosiglitazone was administered to Rip-Cre:mTmG mice, GFP+ cells were not present on the endosteal surface or in the BM of the femur; however, they were present in the pancreas.ConclusionBLCs could be sources of BMAds, and rosiglitazone could stimulate the differentiation of osteoblast lineage cells into BMAds. Suppression of the differentiation of osteoblast lineage cells into BMAds might contribute to anabolic effects resulting from the pharmacologic inhibition of sclerostin.Ji Yeon LeeJi Yeon LeeJae-Yeon YangJae-Yeon YangSang Wan KimSang Wan KimFrontiers Media S.A.articlebone marrow adipocytebone lining cellanti-sclerostin antibodyrosiglitazoneosteoblastDiseases of the endocrine glands. Clinical endocrinologyRC648-665ENFrontiers in Endocrinology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	bone marrow adipocyte bone lining cell anti-sclerostin antibody rosiglitazone osteoblast Diseases of the endocrine glands. Clinical endocrinology RC648-665
spellingShingle	bone marrow adipocyte bone lining cell anti-sclerostin antibody rosiglitazone osteoblast Diseases of the endocrine glands. Clinical endocrinology RC648-665 Ji Yeon Lee Ji Yeon Lee Jae-Yeon Yang Jae-Yeon Yang Sang Wan Kim Sang Wan Kim Bone Lining Cells Could Be Sources of Bone Marrow Adipocytes
description	BackgroundRecently, lineage-tracing studies demonstrated that parathyroid hormone and anti-sclerostin antibody (Scl-Ab) can convert bone lining cells (BLCs) into active osteoblasts. However, BLCs might also be differentiated into other lineages. Here we investigated whether BLCs could differentiate into bone marrow adipocytes (BMAds) and whether Scl-Ab could suppress this process.MethodsDmp1-CreERt2:mTmG mice were injected with 0.5 mg of 4-hydroxytamoxifen once weekly from postnatal week 4 to week 8. The mice were treated with either vehicle or rosiglitazone for 8 weeks (weeks 12–20). Moreover, they were administered either vehicle or Scl-Ab (50 mg/kg) twice weekly for 4 weeks (weeks 16–20, N = 4–6/group). We chased the GFP+ cells from the endosteal surface to the bone marrow (BM) of the femur. Using immunohistochemical staining, the numbers of perilipin+ or GFP+/perilipin double+ cells in the BM were quantified. In addition, serum N-terminal propeptide of type I procollagen (P1NP) levels were measured at each time point, and bone mass was analyzed at 20 weeks using micro-computed tomography.ResultsScl-Ab administration significantly reversed the decreases in bone parameters induced by rosiglitazone. Plump GFP+ cells, presumably active osteoblasts, and extremely flat GFP+ cells, presumably BLCs, were present on the endosteal surface of the femur at 8 and 12 weeks, respectively, in line with prior findings. When we chased the GFP+ cells, rosiglitazone significantly increased the number of GFP/perilipin double+ BMAds compared to the effects of the vehicle (P < 0.001), and overlapping Scl-Ab administration decreased the number of GFP/perilipin double + BMAd compared to rosiglitazone alone (P < 0.001). In addition, we found that osteoblast lineage cells such as BLCs might express PPARγ on immunohistochemical staining. When rosiglitazone was administered to Rip-Cre:mTmG mice, GFP+ cells were not present on the endosteal surface or in the BM of the femur; however, they were present in the pancreas.ConclusionBLCs could be sources of BMAds, and rosiglitazone could stimulate the differentiation of osteoblast lineage cells into BMAds. Suppression of the differentiation of osteoblast lineage cells into BMAds might contribute to anabolic effects resulting from the pharmacologic inhibition of sclerostin.
format	article
author	Ji Yeon Lee Ji Yeon Lee Jae-Yeon Yang Jae-Yeon Yang Sang Wan Kim Sang Wan Kim
author_facet	Ji Yeon Lee Ji Yeon Lee Jae-Yeon Yang Jae-Yeon Yang Sang Wan Kim Sang Wan Kim
author_sort	Ji Yeon Lee
title	Bone Lining Cells Could Be Sources of Bone Marrow Adipocytes
title_short	Bone Lining Cells Could Be Sources of Bone Marrow Adipocytes
title_full	Bone Lining Cells Could Be Sources of Bone Marrow Adipocytes
title_fullStr	Bone Lining Cells Could Be Sources of Bone Marrow Adipocytes
title_full_unstemmed	Bone Lining Cells Could Be Sources of Bone Marrow Adipocytes
title_sort	bone lining cells could be sources of bone marrow adipocytes
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/0a84f972ec5e4da1b35d35b14a99ce09
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Bone Lining Cells Could Be Sources of Bone Marrow Adipocytes

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