Mesenchymal stem cells from osteoporotic patients produce a type I collagen-deficient extracellular matrix favoring adipogenic differentiation

Mesenchymal stem cells (MSCs), precursor cells resident in the bone marrow, have the capacity to differentiate into bone, cartilage, fat, and connecti ve tissue. We have recently reported that MSCs from "healthy" donors differ from cells obtained from osteoporotic postmenopausal women in their prolif eration rate, mitogenic response to osteogenic growth factors, and potentia l to mineralize. The purpose of this study was to examine the factors that explain the differential capacity of MSCs derived from "healthy" control an d osteoporotic postmenopausal women to support mineralization. In addition, we examined the factors that regulate the differentiation of osteoporotic cells into adipocytes. For this purpose, Lye isolated MSCs from bone marrow of donors and analyzed the synthesis and deposition of type I collagen, th e main component of bone extracellular matrix, the time course of gelatinol ytic activity expression, the deposition of transforming growth factor beta (TGF-beta), and the ability of cells to differentiate into adipocytes. Our results indicate that cells derived from osteoporotic donors synthesized 5 0% less type I collagen than normal cells and maintained higher levels of g elatinolytic activity under differentiation conditions (70% versus 15% afte r 14 days in culture). MSCs derived from osteoporotic women produced 60-65% less TGF-beta and expressed higher adipogenic capacity. We conclude that t he capacity of MSCs derived from osteoporotic postmenopausal women to gener ate and maintain type I collagen-rich extracellular matrix is decreased, fa voring their adipogenic differentiation. These observations may explain the decreased mineralization previously observed in these types of cells. (C) 2000 Wiley-Liss, Inc.