Gene expression analysis of major lineage‐defining factors in human bone marrow cells: Effect of aging, gender, and age‐related disorders

Abstract

Adult bone marrow cells (BMCs) include two populations:;mesenchymal stem cells (MSCs), which can differentiate into bone, cartilage, and fat; and hematopoietic stem cells (HSCs), which produce all mature blood lineage. To study the effect of aging, gender, and agerelated disorders on lineage differentiation, we performed quantitative RT-PCR to examine mRNA expression of the major factors defining BMC lineage, cbfa1 for osteoblasts, ppar-gamma for adipocytes, sox9 for chondrocytes, and rankl for osteoclasts, in bone marrow from 80 healthy subjects and patients (14-79 years old) with two age-related disorders: osteoarthritis (OA) and rheumatoid arthritis (RA). Two apoptosis-related genes, bcl-2 and drak1, were studied. RANKL and PPAR-Gamma levels exhibited a clear positive correlation with age in female patients, but not in males, with a slight age-related decline in CBFa1 transcripts. DRAK1 expression showed an age-associated ascending trend with significantly greater transcripts of RANKL and DRAK1 in females ( p < 0.01). Compared with age-matched controls, RA patients exhibited increased RANKL, PPAR-Gamma, and DRAK1 mRNA levels (p < 0.05), and OA showed the higher RANKL and PPARGamma transcripts (p < 0.05). Furthermore, SOX9 and DRAK1 expressions in the RA group were higher than in the OA group (p < 0.05). Our data indicate that aging and age-related disorders affect gene expressions differently, suggesting that in aging, the lineage of bone marrow cells was modified with prominent changes in decreased bone marrow osteoblastogenesis, increased adipogenesis and osteoclastogenesis, while in age-related disorders, marrow adipogenesis and the activity or number of osteoclasts may play an important role in the pathogenesis of arthritic bone loss. ß

Human bone marrow adipocytes support dexamethasone-induced osteoclast differentiation and function through RANKL expression

“…Our study was limited by the fact that the specimens were harvested from patients with osteoarthritis of the hip or femoral neck fracture during prosthetic replacement surgery of the hip joint, so these diseases may have influenced the results. Moreover, the age and sex of the patients, physique, and bone density were not constant, and there may have been individual differences in their response (6,29). However, these issues do not cause us to doubt that factors related to bone metabolism are secreted by bone marrow adipocytes, and that these may have a significant effect on the body.…”

Senescence‐associated intrinsic mechanisms of osteoblast dysfunctions

“…Histomorphometric studies indicate that the age-related decrease in bone mass in mice is associated with increased osteoblastic and osteocytic apoptosis that may be caused by enhanced oxidative stress with age (Almeida et al, 2007). In one human study, no age-related changes in gene expression level of Bcl-2 (a marker for apoptosis) were detected in MSC obtained from 80 healthy subjects (Jiang et al, 2008), but in a recent study, Zhou et al (2008) reported a age-related increase in the number of apoptotic cells in MSC cultures. These discrepancies may be related to the sensitivity of the method employed.…”

Age associated communication between cells and matrix: a potential impact on stem cell-based tissue regeneration strategies

“…Meanwhile, expression of peroxisome proliferator active receptor gamma (PPARG), an adipogenic transcription factor, increased nearly fourfold and SRY (sex determining region Y)-box 9(SOX9, the master regulator of chondrogenesis) was unchanged. 37 Kasper et al studied the changes in SD rat BMSC proteomes associated with aging, and attributed the inverse correlation between age and replicative potential in part to a decline in cellular responsiveness to mechanical stimuli resulting from a less dynamic actin cytoskeleton. 38 Veronesi and coworkers reviewed studies on aging's effects on ADSCs and BMSCs, and concluded that, although some authors found no differences in the proliferative capacity of MSCs, the majority of studies agreed that decreases in MSC proliferation rate and osteogenic capacity were observed with age.…”