Transplantation of bone marrow-derived mesenchymal stem cells rescues partially rachitic phenotypes induced by 1,25-Dihydroxyvitamin D deficiency in mice.
To determine whether the transplantation of bone marrow-derived mesenchymal stem cells (BM-MSCs) can improve the 1,25(OH)2D deficiency-induced rachitic phenotype, 2×106BM-MSCs from wild-type mice or vehicle were transplanted by tail vein injection into mice deficient in 1,25(OH)2D due to targeted deletion of 1α(OH)ase (1α(OH)ase-/-). Our results show that 1α(OH)ase mRNA was expressed in the BM-MSCs derived from wild-type mice, and was detected in long bone, kidney and intestine from BM-MSC-transplanted 1α(OH)ase-/-recipients. Serum calcium, 1,25(OH)2D3levels and body weight were significantly increased in BM-MSC-transplanted 1α(OH)ase-/-recipients compared to vehicle-treated 1α(OH)ase-/-mice. Skeletal mineralization improved in 1α(OH)ase-/-recipients as demonstrated by BMD measurement, micro-CT analysis and von Kossa staining of undecalcified sections. Expression levels of type I collagen, osteocalcin, bone sialoprotein and vitronectin and the size of calcified nodules were decreased in BM-MSC cultures from 1α(OH)ase-/-mice compared with those from wild-type mice, however, these parameters were increased in those from BM-MSCs-transplanted 1α(OH)ase-/-recipients compared with those from vehicle-treated 1α(OH)ase-/-mice. This study indicates that donor BM-MSCs cells can relocate to multiple tissues where they synthesize 1α(OH)ase and produce 1,25(OH)2D that contributes to the improvement of serum calcium and skeletal mineralization. Results from this study suggest that BM-MSC transplantation may provide a therapeutic approach to treatment of pseudovitamin D-deficiency rickets.
Department of Public Health, Soochow University Suzhou, Jiangsu, China.
Zengli
Z
Zhang
Department of Orthopedics, Aoyang Hospital Zhangjiagang, Jiangsu, China.
Shaomeng
S
Yin
The State Key Laboratory of Reproductive Medicine, The Research Center for Bone and Stem Cells, Nanjing Medical University Nanjing, Jiangsu, China.
Xian
X
Xue
The State Key Laboratory of Reproductive Medicine, The Research Center for Bone and Stem Cells, Nanjing Medical University Nanjing, Jiangsu, China.
Ji
J
Ji
Department of Public Health, Soochow University Suzhou, Jiangsu, China.
Jian
J
Tong
Calcium Research Laboratory, McGill University Health Centre and Department of Medicine, McGill University Montreal, Quebec, Canada.
David
D
Goltzman
The State Key Laboratory of Reproductive Medicine, The Research Center for Bone and Stem Cells, Nanjing Medical University Nanjing, Jiangsu, China.
Dengshun
D
Miao
1α-hydroxylase; Bone marrow mesenchymal stem cells; pseudovitamin D-deficiency rickets; transplantation