Bone Morphogenetic Protein‐6 Attenuates Type 1 Diabetes Mellitus‐Associated Bone Loss

Autor: Ming-Song Lee, Matthew W. Squire, Darrin J. Trask, Ellen M. Leiferman, Jesse F Wang, Tsung-Lin Tsai, Wan-Ju Li
Jazyk: angličtina
Rok vydání: 2019
Předmět:
0301 basic medicine
endocrine system diseases
Bone Morphogenetic Protein 6
medicine.medical_treatment
Osteoporosis
Bone morphogenetic protein‐6
Mice
0302 clinical medicine
Bone Density
immune system diseases
Osteogenesis
Mesenchymal stem cell
Bone mineral
lcsh:R5-920
lcsh:Cytology
Cell Differentiation
General Medicine
Recombinant Proteins
3. Good health
Bone morphogenetic protein 6
Stem cell
lcsh:Medicine (General)
medicine.medical_specialty
Bone loss
Intraperitoneal injection
Type 1 diabetes mellitus
Bone Morphogenetic Protein Receptors
Type II
Mesenchymal Stem Cell Transplantation
Bone and Bones
Diabetes Mellitus
Experimental
03 medical and health sciences
Internal medicine
medicine
Animals
lcsh:QH573-671
Type 1 diabetes
business.industry
Receptor
Transforming Growth Factor-beta Type II
nutritional and metabolic diseases
Mesenchymal Stem Cells
Cell Biology
X-Ray Microtomography
medicine.disease
Osteopenia
Mice
Inbred C57BL
Bone Diseases
Metabolic
030104 developmental biology
Endocrinology
Diabetes Mellitus
Type 1
Hyperglycemia
business
human activities
030217 neurology & neurosurgery
Developmental Biology
Tissue‐Specific Progenitor and Stem Cells
Zdroj: Stem Cells Translational Medicine, Vol 8, Iss 6, Pp 522-534 (2019)
Stem Cells Translational Medicine
ISSN: 2157-6564
2157-6580
Popis: Patients with type 1 diabetes mellitus (T1DM) often suffer from osteopenia or osteoporosis. Although most agree that T1DM-induced hyperglycemia is a risk factor for progressive bone loss, the mechanisms for the link between T1DM and bone loss still remain elusive. In this study, we found that bone marrow-derived mesenchymal stem cells (BMSCs) isolated from T1DM donors were less inducible for osteogenesis than those from non-T1DM donors and further identified a mechanism involving bone morphogenetic protein-6 (BMP6) that was produced significantly less in BMSCs derived from T1DM donors than that in control cells. With addition of exogenous BMP6 in culture, osteogenesis of BMSCs from T1DM donors was restored whereas the treatment of BMP6 seemed not to affect non-T1DM control cells. We also demonstrated that bone mineral density (BMD) was reduced in streptozotocin-induced diabetic mice compared with that in control animals, and intraperitoneal injection of BMP6 mitigated bone loss and increased BMD in diabetic mice. Our results suggest that bone formation in T1DM patients is impaired by reduction of endogenous BMP6, and supplementation of BMP6 enhances osteogenesis of BMSCs to restore BMD in a mouse model of T1DM, which provides insight into the development of clinical treatments for T1DM-assocaited bone loss. Stem Cells Translational Medicine 2019;8:522–534
Databáze: OpenAIRE
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