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Transplantation of mesenchymal stem cells ameliorates secondary osteoporosis through interleukin-17-impaired functions of recipient bone marrow mesenchymal stem cells in MRL/lpr mice.
- Source :
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Stem cell research & therapy [Stem Cell Res Ther] 2015 May 27; Vol. 6, pp. 104. Date of Electronic Publication: 2015 May 27. - Publication Year :
- 2015
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Abstract
- Introduction: Secondary osteoporosis is common in systemic lupus erythematosus and leads to a reduction in quality of life due to fragility fractures, even in patients with improvement of the primary disorder. Systemic transplantation of mesenchymal stem cells could ameliorate bone loss and autoimmune disorders in a MRL/lpr mouse systemic lupus erythematosus model, but the detailed therapeutic mechanism of bone regeneration is not fully understood. In this study, we transplanted human bone marrow mesenchymal stem cells (BMMSCs) and stem cells from exfoliated deciduous teeth (SHED) into MRL/lpr mice and explored their therapeutic mechanisms in secondary osteoporotic disorders of the systemic lupus erythematosus model mice.<br />Methods: The effects of systemic human mesenchymal stem cell transplantation on bone loss of MRL/lpr mice were analyzed in vivo and ex vivo. After systemic human mesenchymal stem cell transplantation, recipient BMMSC functions of MRL/lpr mice were assessed for aspects of stemness, osteogenesis and osteoclastogenesis, and a series of co-culture experiments under osteogenic or osteoclastogenic inductions were performed to examine the efficacy of interleukin (IL)-17-impaired recipient BMMSCs in the bone marrow of MRL/lpr mice.<br />Results: Systemic transplantation of human BMMSCs and SHED recovered the reduction in bone density and structure in MRL/lpr mice. To explore the mechanism, we found that impaired recipient BMMSCs mediated the negative bone metabolic turnover by enhanced osteoclastogenesis and suppressed osteoblastogenesis in secondary osteoporosis of MRL/lpr mice. Moreover, IL-17-dependent hyperimmune conditions in the recipient bone marrow of MRL/lpr mice damaged recipient BMMSCs to suppress osteoblast capacity and accelerate osteoclast induction. To overcome the abnormal bone metabolism, systemic transplantation of human BMMSCs and SHED into MRL/lpr mice improved the functionally impaired recipient BMMSCs through IL-17 suppression in the recipient bone marrow and then maintained a regular positive bone metabolism via the balance of osteoblasts and osteoclasts.<br />Conclusions: These findings indicate that IL-17 and recipient BMMSCs might be a therapeutic target for secondary osteoporosis in systemic lupus erythematosus.
- Subjects :
- Animals
Antibodies immunology
Antibodies pharmacology
Bone Marrow Cells cytology
Bone Marrow Cells metabolism
Cells, Cultured
Child
Child, Preschool
Coculture Techniques
Female
Femur diagnostic imaging
Femur pathology
Humans
Interleukin-17 immunology
Interleukin-17 pharmacology
Lupus Erythematosus, Systemic complications
Lupus Erythematosus, Systemic therapy
Mesenchymal Stem Cells metabolism
Mice
Mice, Inbred C57BL
Mice, Inbred MRL lpr
Osteogenesis drug effects
Osteoporosis complications
Radiography
Skull cytology
Skull metabolism
Th17 Cells cytology
Th17 Cells immunology
Th17 Cells metabolism
Interleukin-17 metabolism
Mesenchymal Stem Cell Transplantation
Mesenchymal Stem Cells cytology
Osteoporosis therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1757-6512
- Volume :
- 6
- Database :
- MEDLINE
- Journal :
- Stem cell research & therapy
- Publication Type :
- Academic Journal
- Accession number :
- 26012584
- Full Text :
- https://doi.org/10.1186/s13287-015-0091-4