3′-Sialyllactose alleviates bone loss by regulating bone homeostasis

Abstract Osteoporosis is a common skeletal disease that results in an increased risk of fractures. However, there is no definitive cure, warranting the development of potential therapeutic agents. 3′-Sialyllactose (3′-SL) in human milk regulates many biological functions. However, its effect on bone...

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Main Authors: Ahreum Baek, Dawoon Baek, Yoonhee Cho, Seongmoon Jo, Jinyoung Kim, Yoontaik Hong, Seunghee Cho, Sung Hoon Kim, Sung-Rae Cho
Format: Article
Language:English
Published: Nature Portfolio 2024-01-01
Series:Communications Biology
Online Access:https://doi.org/10.1038/s42003-024-05796-4
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author Ahreum Baek
Dawoon Baek
Yoonhee Cho
Seongmoon Jo
Jinyoung Kim
Yoontaik Hong
Seunghee Cho
Sung Hoon Kim
Sung-Rae Cho
author_facet Ahreum Baek
Dawoon Baek
Yoonhee Cho
Seongmoon Jo
Jinyoung Kim
Yoontaik Hong
Seunghee Cho
Sung Hoon Kim
Sung-Rae Cho
author_sort Ahreum Baek
collection DOAJ
description Abstract Osteoporosis is a common skeletal disease that results in an increased risk of fractures. However, there is no definitive cure, warranting the development of potential therapeutic agents. 3′-Sialyllactose (3′-SL) in human milk regulates many biological functions. However, its effect on bone metabolism remains unknown. This study aimed to investigate the molecular mechanisms underlying the effect of 3′-SL on bone homeostasis. Treatment of human bone marrow stromal cells (hBMSCs) with 3′-SL enhanced osteogenic differentiation and inhibited adipogenic differentiation of hBMSCs. RNA sequencing showed that 3′-SL enhanced laminin subunit gamma-2 expression and promoted osteogenic differentiation via the phosphatidylinositol 3‑kinase/protein kinase B signaling pathway. Furthermore, 3′-SL inhibited the receptor activator of nuclear factor κB ligand-induced osteoclast differentiation of bone marrow-derived macrophages through the nuclear factor κB and mitogen‑activated protein kinase signaling pathway, ameliorated osteoporosis in ovariectomized mice, and positively regulated bone remodeling. Our findings suggest 3′-SL as a potential drug for osteoporosis.
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spelling doaj.art-b03ed7a36cbb4187903391d5852d30702024-01-21T12:30:49ZengNature PortfolioCommunications Biology2399-36422024-01-017111510.1038/s42003-024-05796-43′-Sialyllactose alleviates bone loss by regulating bone homeostasisAhreum Baek0Dawoon Baek1Yoonhee Cho2Seongmoon Jo3Jinyoung Kim4Yoontaik Hong5Seunghee Cho6Sung Hoon Kim7Sung-Rae Cho8Department of Rehabilitation Medicine, Yonsei University Wonju College of MedicineDepartment of Rehabilitation Medicine, Yonsei University Wonju College of MedicineDepartment of Medicine, Yonsei University College of MedicineDepartment of Rehabilitation Medicine, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of MedicineDepartment of Rehabilitation Medicine, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of MedicineAAVATAR TherapeuticsAAVATAR TherapeuticsDepartment of Rehabilitation Medicine, Yonsei University Wonju College of MedicineDepartment of Rehabilitation Medicine, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of MedicineAbstract Osteoporosis is a common skeletal disease that results in an increased risk of fractures. However, there is no definitive cure, warranting the development of potential therapeutic agents. 3′-Sialyllactose (3′-SL) in human milk regulates many biological functions. However, its effect on bone metabolism remains unknown. This study aimed to investigate the molecular mechanisms underlying the effect of 3′-SL on bone homeostasis. Treatment of human bone marrow stromal cells (hBMSCs) with 3′-SL enhanced osteogenic differentiation and inhibited adipogenic differentiation of hBMSCs. RNA sequencing showed that 3′-SL enhanced laminin subunit gamma-2 expression and promoted osteogenic differentiation via the phosphatidylinositol 3‑kinase/protein kinase B signaling pathway. Furthermore, 3′-SL inhibited the receptor activator of nuclear factor κB ligand-induced osteoclast differentiation of bone marrow-derived macrophages through the nuclear factor κB and mitogen‑activated protein kinase signaling pathway, ameliorated osteoporosis in ovariectomized mice, and positively regulated bone remodeling. Our findings suggest 3′-SL as a potential drug for osteoporosis.https://doi.org/10.1038/s42003-024-05796-4
spellingShingle Ahreum Baek
Dawoon Baek
Yoonhee Cho
Seongmoon Jo
Jinyoung Kim
Yoontaik Hong
Seunghee Cho
Sung Hoon Kim
Sung-Rae Cho
3′-Sialyllactose alleviates bone loss by regulating bone homeostasis
Communications Biology
title 3′-Sialyllactose alleviates bone loss by regulating bone homeostasis
title_full 3′-Sialyllactose alleviates bone loss by regulating bone homeostasis
title_fullStr 3′-Sialyllactose alleviates bone loss by regulating bone homeostasis
title_full_unstemmed 3′-Sialyllactose alleviates bone loss by regulating bone homeostasis
title_short 3′-Sialyllactose alleviates bone loss by regulating bone homeostasis
title_sort 3 sialyllactose alleviates bone loss by regulating bone homeostasis
url https://doi.org/10.1038/s42003-024-05796-4
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