The Effects of Aging on the Proliferation and Differentiation of Osteoblasts from Human Mesenchymal Stem Cells.
- Author:
Ki Hyun BAEK
1
;
Hyun Jung TAE
;
Ki Won OH
;
Won Young LEE
;
Chung Kee CHO
;
Soon Yong KWON
;
Moo Il KANG
;
Bong Yun CHA
;
Kwang Woo LEE
;
Ho Young SON
;
Sung Koo KANG
;
Choon Choo KIM
Author Information
1. Department of Internal Medicine, The Catholic University of Korea, College of Medicine.
- Publication Type:Original Article
- Keywords:
Aging;
Mesenchymal stem cell;
Bone marrow stromal cell;
Proliferation;
Differentiation Cushing's syndrome;
Insulin sensitivity;
Insulin secretion
- MeSH:
Aging*;
Alkaline Phosphatase;
Bone Marrow;
Cell Count;
Humans*;
Insulin Resistance;
Mesenchymal Stromal Cells*;
Osteoblasts*;
Osteocalcin;
Tissue Donors
- From:Journal of Korean Society of Endocrinology
2003;18(3):296-305
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
BACKGROUND: Osteoblasts originate from osteoprogenitor cells in bone marrow stroma, termed mesenchymal stem cells (MSCs) or bone marrow stromal cells. Each MSC forms colonies (colony forming units-fibroblasts [CFU-Fs]) when cultured ex vivo. There are some reports about the age-related changes of the number and osteogenic potential of osteoprogenitor cells, but any relationship has not been clearly established in humans. In this study, we counted MSCs using CFU-Fs count and examined the proliferative capacity and differentiation potential of osteoprogenitor cells. Finally, we analyzed how these parameters varied with donor age. METHODS: Bone marrow was obtained from the iliac crest of young (n=6, 27.2+/-8.6 years old) and old (n=10, 57.4+/-6.7 years old) healthy donors. Mononuclear cells, including MSCs, were isolated and cultured in osteogenic medium. In primary culture, we compared the colony-forming efficiency of MSCs between the two groups and determined the matrix calcification. When primary culture showed near confluence, the cells were subcultured. Alkaline phosphatase activity, osteocalcinexpression by RT-PCR and proliferative potential by MTT assay were examined by the time course of secondary culture. RESULTS: At the 15th day of primary culture, the mean number of CFU-Fs was significantly higher in the younger donors (young: 148.3+/-28.9, old: 54.3+/-9.1, p=0.02) and the mean size of CFU-Fs was also larger in the younger donors than the older donors. However, matrix calcification was not different between the two groups (young: 103.6+/-50.6, old: 114.0+/-56.5, p=NS). In secondary culture, alkaline phosphatase activities were significantly lower in the older donors. The younger donors showed peak alkaline phosphatase activity at day 10, while the older donors didn't showed a remarkable peak (young: 935.5+/-115.0U/mg, old: 578.4+/-115.7U/mg, p<0.05). Total cell number as a proliferative index increased progressively during the secondary culture and a significantly greater cell number was noted in the younger donors. Osteocalcin expression was generally upregulated in the younger donors, but this was not statistically significant. CONCLUSION: Our study shows that the number of osteoprogenitor cells is decreased during aging and that the proliferative capacity and differentiation potential of osteoprogenitor cells seem to be reduced during aging.