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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 373-386 |
| Number of pages | 14 |
| Journal | Stem Cell Reports |
| Volume | 8 |
| Issue number | 2 |
| DOIs | |
| State | Published - Feb 14 2017 |
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Keywords
- adipocyte
- bone marrow stromal cells
- differentiation
- extracellular matrix
- fibronectin
- legumain
- mesenchymal stem cell
- osteoblast
- osteoporosis
- proliferation
ASJC Scopus subject areas
- Biochemistry
- Genetics
- Developmental Biology
- Cell Biology
Cite this
Legumain Regulates Differentiation Fate of Human Bone Marrow Stromal Cells and Is Altered in Postmenopausal Osteoporosis. / Jafari, Abbas; Qanie, Diyako; Andersen, Thomas L.; Zhang, Yuxi; Chen, Li; Postert, Benno; Parsons, Stuart; Ditzel, Nicholas; Khosla, Sundeep; Johansen, Harald Thidemann; Kjærsgaard-Andersen, Per; Delaisse, Jean Marie; Abdallah, Basem M.; Hesselson, Daniel; Solberg, Rigmor; Kassem, Moustapha.
In: Stem Cell Reports, Vol. 8, No. 2, 14.02.2017, p. 373-386.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Legumain Regulates Differentiation Fate of Human Bone Marrow Stromal Cells and Is Altered in Postmenopausal Osteoporosis
AU - Jafari, 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.
KW - adipocyte
KW - bone marrow stromal cells
KW - differentiation
KW - extracellular matrix
KW - fibronectin
KW - legumain
KW - mesenchymal stem cell
KW - osteoblast
KW - osteoporosis
KW - proliferation
UR - http://www.scopus.com/inward/record.url?scp=85011309742&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85011309742&partnerID=8YFLogxK
U2 - 10.1016/j.stemcr.2017.01.003
DO - 10.1016/j.stemcr.2017.01.003
M3 - Article
C2 - 28162997
AN - SCOPUS:85011309742
VL - 8
SP - 373
EP - 386
JO - Stem Cell Reports
JF - Stem Cell Reports
SN - 2213-6711
IS - 2
ER -