Age-Related Changes in the Osteogenic Differentiation Potential of Mouse Bone Marrow Stromal Cells

Abstract

Age-dependent bone loss has been well documented in both human and animal models. Although the underlying causal mechanisms are probably multifactorial, it has been hypothesized that alterations in progenitor cell number or function are important. Little is known regarding the properties of bone marrow stromal cells (BMSCs) or bone progenitor cells during the aging process, so the question of whether aging alters BMSC/progenitor osteogenic differentiation remains unanswered. In this study, we examined agedependent changes in bone marrow progenitor cell number and differentiation potential between mature (3 and 6 mo old), middle-aged (12 and 18 mo old), and aged (24 mo old) C57BL/6 mice. BMSCs or progenitors were isolated from five age groups of C57BL/6 mice using negative immunodepletion and positive immunoselection approaches. The osteogenic differentiation potential of multipotent BMSCs was determined using standard osteogenic differentiation procedures. Our results show that both BMSC/progenitor number and differentiation potential increase between the ages of 3 and 18 mo and decrease rapidly thereafter with advancing age. These results are consistent with the changes of the mRNA levels of osteoblast lineageassociated genes. Our data suggest that the decline in BMSC number and osteogenic differentiation capacity are important factors contributing to age-related bone loss.

Age-related Marrow Adipogenesis Is Linked to Increased Expression of RANKL

“…We also found that osteoclast colonies are markedly increased in bone marrow cultures from aged mice, especially when they are induced toward adipogenic differentiation, and that they survived for several months. Although it is generally recognized that osteoblastogenesis decreases with aging, it has also been reported that CFU-F increases and CFU-Ob remains unaltered or even increases until 18 months old in mice (40,41), implying that differences in culture conditions and the sex and age of animals used are important.…”

Stromal Cell-Derived Factor-1β Potentiates Bone Morphogenetic Protein-2-Stimulated Osteoinduction of Genetically Engineered Bone Marrow-Derived Mesenchymal Stem CellsIn Vitro

“…The isolation process, negative immunodepletion (CD11b, CD45R/B220, CD11c, plasmacytoid dendritic cell antigen-1 [PDCA-1]), positive immunoselection (stem cell antigen-1 [Sca-1]), and retroviral infection (GFP) have been described previously. 28,29 First, six mice per age group were euthanized by CO 2 overdose followed by thoracotomy. The femora and tibiae were dissected free of soft tissues and kept in cold PBS on ice.…”

“…Resulting CD11b, CD45R/B220, CD11c, PDCA-1-negative cells were subjected to positive immunoselection using antiSca-1 microbeads (Miltenyi Biotec) following the manufacturer's recommendations. Enriched BMSCs (3 months: 1.35% CD45, 1.45% CD11b, 74.46% Sca-1; 18 months: 0.33% CD45, 0.13% CD11b, 83.18% Sca-1 by FACS analysis 28 ), which are depleted of monocytes, granulocytes, macrophages, myeloid-derived dendritic cells (DCs), natural killer cells, B-1 cells, B lymphocytes, T lymphocytes, classical DCs, plasmacytoid DCs, and macrophage progenitors, were maintained in the Dulbecco's modified Eagle's medium (DMEM; Cellgro) with 10% heat-inactivated FBS (Atlanta Biologicals), and shown of possessing multilineage potential. 28 Of note, BMSCs derived from 3-month-old animals at this stage were used for comparisons with whole BM cell isolates (see above) derived from a second set of 3-monthold mice.…”

Triiodotironina não aumenta a diferenciação osteogênica reduzida pela idade de células-tronco mesenquimais da medula óssea de ratas

“…Esse resultado foi semelhante ao observado por outros estudos (11)(12)(13)(14)(15)17,18). Segundo Hell e cols.…”

“…Contudo, tanto em animais quanto em seres humanos a diferenciação osteogênica das CTM-MO pode ser comprometida pela idade ou por doenças como a osteoporose e as disfunções tireoidianas, entre outras (11)(12)(13)(14)(15)(16)(17)(18). Assim, o efeito da idade poderia limitar o uso da terapia com células-tronco autólogas em pacientes adultos ou idosos.…”