Gene expression analysis of major lineage-defining factors in human bone marrow cells: effect of aging, gender, and age-related disorders.
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 age-related 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 PPAR-Gamma 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.
Jiang
Ying
Y
Nanotechnology Research Institute (NRI), National Institute of Advanced Industrial Science and Technology (AIST), 1-1-1 Higashi, Tsukuba, Ibaraki 305-8566, Japan.
Mishima
Hajime
H
Sakai
Shinsuke
S
Liu
Yin-Kun
YK
Ohyabu
Yoshimi
Y
Uemura
Toshimasa
T
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D017209:Apoptosis / Q000502:physiology; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D001172:Arthritis, Rheumatoid / Q000209:etiology / Q000378:metabolism*; D001853:Bone Marrow / Q000378:metabolism*; D016022:Case-Control Studies; D002454:Cell Differentiation / Q000502:physiology*; D019070:Cell Lineage / Q000502:physiology; D050659:Core Binding Factor Alpha 1 Subunit / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006609:High Mobility Group Proteins / Q000378:metabolism; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D008875:Middle Aged; D010003:Osteoarthritis / Q000209:etiology / Q000378:metabolism*; D047495:PPAR gamma / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D053245:RANK Ligand / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055758:SOX9 Transcription Factor; D012737:Sex Factors; D014157:Transcription Factors / Q000378:metabolism
D051017:Apoptosis Regulatory Proteins; D050659:Core Binding Factor Alpha 1 Subunit; D006609:High Mobility Group Proteins; D047495:PPAR gamma; D019253:Proto-Oncogene Proteins c-bcl-2; D053245:RANK Ligand; D055758:SOX9 Transcription Factor; C527932:SOX9 protein, human; C505688:TNFSF11 protein, human; D014157:Transcription Factors; D017346:Protein Serine-Threonine Kinases; C115488:STK17A protein, human