Legumain Regulates Differentiation Fate of Human Bone Marrow Stromal Cells and Is Altered in Postmenopausal Osteoporosis

Abbas Jafari Kermani; Diyako Qanie; Thomas L Andersen; Yuxi Zhang; Li Chen; Benno Postert; Stuart Parsons; Nicholas Ditzel; Sundeep Khosla; Harald Thidemann Johansen; Per Kjærsgaard-Andersen; Jean-Marie Delaisse; Basem M Abdallah; Daniel Hesselson; Rigmor Solberg; Moustapha Kassem

doi:10.1016/j.stemcr.2017.01.003

Legumain Regulates Differentiation Fate of Human Bone Marrow Stromal Cells and Is Altered in Postmenopausal Osteoporosis

Abbas Jafari Kermani, Diyako Qanie, Thomas L Andersen, Yuxi Zhang, Li Chen, Benno Postert, Stuart Parsons, Nicholas Ditzel, Sundeep Khosla, Harald Thidemann Johansen, Per Kjærsgaard-Andersen, Jean-Marie Delaisse, Basem M Abdallah, Daniel Hesselson, Rigmor Solberg, Moustapha Kassem

Morphogenesis and Differentiation Program

35 Citationer (Scopus)

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Abstract

Secreted factors are a key component of stem cell niche and their dysregulation compromises stem cell function. Legumain is a secreted cysteine protease involved in diverse biological processes. Here, we demonstrate that legumain regulates lineage commitment of human bone marrow stromal cells and that its expression level and cellular localization are altered in postmenopausal osteoporotic patients. As shown by genetic and pharmacological manipulation, legumain inhibited osteoblast (OB) differentiation and in vivo bone formation through degradation of the bone matrix protein fibronectin. In addition, genetic ablation or pharmacological inhibition of legumain activity led to precocious OB differentiation and increased vertebral mineralization in zebrafish. Finally, we show that localized increased expression of legumain in bone marrow adipocytes was inversely correlated with adjacent trabecular bone mass in a cohort of patients with postmenopausal osteoporosis. Our data suggest that altered proteolytic activity of legumain in the bone microenvironment contributes to decreased bone mass in postmenopausal osteoporosis.

Originalsprog	Engelsk
Tidsskrift	Stem Cell Reports
Vol/bind	8
Udgave nummer	2
Sider (fra-til)	373-386
Antal sider	14
ISSN	2213-6711
DOI	https://doi.org/10.1016/j.stemcr.2017.01.003
Status	Udgivet - 14 feb. 2017

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10.1016/j.stemcr.2017.01.003Licens: CC BY-NC-ND

Legumain Regulates Differentiation Fate of Human Bone Marrow Stromal Cells and Is Altered in Postmenopausal OsteoporosisForlagets udgivne version, 3,83 MBLicens: CC BY-NC-ND

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Jafari Kermani, A., Qanie, D., Andersen, T. L., Zhang, Y., Chen, L., Postert, B., Parsons, S., Ditzel, N., Khosla, S., Johansen, H. T., Kjærsgaard-Andersen, P., Delaisse, J.-M., Abdallah, B. M., Hesselson, D., Solberg, R., & Kassem, M. (2017). Legumain Regulates Differentiation Fate of Human Bone Marrow Stromal Cells and Is Altered in Postmenopausal Osteoporosis. Stem Cell Reports, 8(2), 373-386. https://doi.org/10.1016/j.stemcr.2017.01.003

Jafari Kermani, A, Qanie, D, Andersen, TL, Zhang, Y, Chen, L, Postert, B, Parsons, S, Ditzel, N, Khosla, S, Johansen, HT, Kjærsgaard-Andersen, P, Delaisse, J-M, Abdallah, BM, Hesselson, D, Solberg, R & Kassem, M 2017, 'Legumain Regulates Differentiation Fate of Human Bone Marrow Stromal Cells and Is Altered in Postmenopausal Osteoporosis', Stem Cell Reports, bind 8, nr. 2, s. 373-386. https://doi.org/10.1016/j.stemcr.2017.01.003

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title = "Legumain Regulates Differentiation Fate of Human Bone Marrow Stromal Cells and Is Altered in Postmenopausal Osteoporosis",

abstract = "Secreted factors are a key component of stem cell niche and their dysregulation compromises stem cell function. Legumain is a secreted cysteine protease involved in diverse biological processes. Here, we demonstrate that legumain regulates lineage commitment of human bone marrow stromal cells and that its expression level and cellular localization are altered in postmenopausal osteoporotic patients. As shown by genetic and pharmacological manipulation, legumain inhibited osteoblast (OB) differentiation and in vivo bone formation through degradation of the bone matrix protein fibronectin. In addition, genetic ablation or pharmacological inhibition of legumain activity led to precocious OB differentiation and increased vertebral mineralization in zebrafish. Finally, we show that localized increased expression of legumain in bone marrow adipocytes was inversely correlated with adjacent trabecular bone mass in a cohort of patients with postmenopausal osteoporosis. Our data suggest that altered proteolytic activity of legumain in the bone microenvironment contributes to decreased bone mass in postmenopausal osteoporosis.",

author = "{Jafari Kermani}, Abbas and Diyako Qanie and Andersen, {Thomas L} and Yuxi Zhang and Li Chen and Benno Postert and Stuart Parsons and Nicholas Ditzel and Sundeep Khosla and Johansen, {Harald Thidemann} and Per Kj{\ae}rsgaard-Andersen and Jean-Marie Delaisse and Abdallah, {Basem M} and Daniel Hesselson and Rigmor Solberg and Moustapha Kassem",

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doi = "10.1016/j.stemcr.2017.01.003",

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T1 - Legumain Regulates Differentiation Fate of Human Bone Marrow Stromal Cells and Is Altered in Postmenopausal Osteoporosis

AU - Jafari Kermani, Abbas

AU - Qanie, Diyako

AU - Andersen, Thomas L

AU - Zhang, Yuxi

AU - Chen, Li

AU - Postert, Benno

AU - Parsons, Stuart

AU - Ditzel, Nicholas

AU - Khosla, Sundeep

AU - Johansen, Harald Thidemann

AU - Kjærsgaard-Andersen, Per

AU - Delaisse, Jean-Marie

AU - Abdallah, Basem M

AU - Hesselson, Daniel

AU - Solberg, Rigmor

AU - Kassem, Moustapha

PY - 2017/2/14

Y1 - 2017/2/14

N2 - Secreted factors are a key component of stem cell niche and their dysregulation compromises stem cell function. Legumain is a secreted cysteine protease involved in diverse biological processes. Here, we demonstrate that legumain regulates lineage commitment of human bone marrow stromal cells and that its expression level and cellular localization are altered in postmenopausal osteoporotic patients. As shown by genetic and pharmacological manipulation, legumain inhibited osteoblast (OB) differentiation and in vivo bone formation through degradation of the bone matrix protein fibronectin. In addition, genetic ablation or pharmacological inhibition of legumain activity led to precocious OB differentiation and increased vertebral mineralization in zebrafish. Finally, we show that localized increased expression of legumain in bone marrow adipocytes was inversely correlated with adjacent trabecular bone mass in a cohort of patients with postmenopausal osteoporosis. Our data suggest that altered proteolytic activity of legumain in the bone microenvironment contributes to decreased bone mass in postmenopausal osteoporosis.

AB - Secreted factors are a key component of stem cell niche and their dysregulation compromises stem cell function. Legumain is a secreted cysteine protease involved in diverse biological processes. Here, we demonstrate that legumain regulates lineage commitment of human bone marrow stromal cells and that its expression level and cellular localization are altered in postmenopausal osteoporotic patients. As shown by genetic and pharmacological manipulation, legumain inhibited osteoblast (OB) differentiation and in vivo bone formation through degradation of the bone matrix protein fibronectin. In addition, genetic ablation or pharmacological inhibition of legumain activity led to precocious OB differentiation and increased vertebral mineralization in zebrafish. Finally, we show that localized increased expression of legumain in bone marrow adipocytes was inversely correlated with adjacent trabecular bone mass in a cohort of patients with postmenopausal osteoporosis. Our data suggest that altered proteolytic activity of legumain in the bone microenvironment contributes to decreased bone mass in postmenopausal osteoporosis.

U2 - 10.1016/j.stemcr.2017.01.003

DO - 10.1016/j.stemcr.2017.01.003

M3 - Journal article

C2 - 28162997

SN - 2213-6711

VL - 8

SP - 373

EP - 386

JO - Stem Cell Reports

JF - Stem Cell Reports

IS - 2

ER -

Legumain Regulates Differentiation Fate of Human Bone Marrow Stromal Cells and Is Altered in Postmenopausal Osteoporosis

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