PMID- 18302252 OWN - NLM STAT- MEDLINE DCOM- 20080708 LR - 20211203 IS - 1554-527X (Electronic) IS - 0736-0266 (Linking) VI - 26 IP - 7 DP - 2008 Jul TI - Gene expression analysis of major lineage-defining factors in human bone marrow cells: effect of aging, gender, and age-related disorders. PG - 910-7 LID - 10.1002/jor.20623 [doi] AB - 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. FAU - Jiang, Ying AU - Jiang Y AD - Nanotechnology Research Institute (NRI), National Institute of Advanced Industrial Science and Technology (AIST), 1-1-1 Higashi, Tsukuba, Ibaraki 305-8566, Japan. FAU - Mishima, Hajime AU - Mishima H FAU - Sakai, Shinsuke AU - Sakai S FAU - Liu, Yin-Kun AU - Liu YK FAU - Ohyabu, Yoshimi AU - Ohyabu Y FAU - Uemura, Toshimasa AU - Uemura T LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Orthop Res JT - Journal of orthopaedic research : official publication of the Orthopaedic Research Society JID - 8404726 RN - 0 (Apoptosis Regulatory Proteins) RN - 0 (Core Binding Factor Alpha 1 Subunit) RN - 0 (High Mobility Group Proteins) RN - 0 (PPAR gamma) RN - 0 (Proto-Oncogene Proteins c-bcl-2) RN - 0 (RANK Ligand) RN - 0 (SOX9 Transcription Factor) RN - 0 (SOX9 protein, human) RN - 0 (TNFSF11 protein, human) RN - 0 (Transcription Factors) RN - EC 2.7.11.1 (Protein Serine-Threonine Kinases) RN - EC 2.7.11.1 (STK17A protein, human) SB - IM MH - Adolescent MH - Adult MH - Age Factors MH - Aged MH - Apoptosis/physiology MH - Apoptosis Regulatory Proteins/*metabolism MH - Arthritis, Rheumatoid/etiology/*metabolism MH - Bone Marrow/*metabolism MH - Case-Control Studies MH - Cell Differentiation/*physiology MH - Cell Lineage/physiology MH - Core Binding Factor Alpha 1 Subunit/metabolism MH - Female MH - Gene Expression MH - High Mobility Group Proteins/metabolism MH - Humans MH - Male MH - Mesenchymal Stem Cells/cytology/*metabolism MH - Middle Aged MH - Osteoarthritis/etiology/*metabolism MH - PPAR gamma/metabolism MH - Protein Serine-Threonine Kinases/*metabolism MH - Proto-Oncogene Proteins c-bcl-2/metabolism MH - RANK Ligand/metabolism MH - Reverse Transcriptase Polymerase Chain Reaction MH - SOX9 Transcription Factor MH - Sex Factors MH - Transcription Factors/metabolism EDAT- 2008/02/28 09:00 MHDA- 2008/07/09 09:00 CRDT- 2008/02/28 09:00 PHST- 2008/02/28 09:00 [pubmed] PHST- 2008/07/09 09:00 [medline] PHST- 2008/02/28 09:00 [entrez] AID - 10.1002/jor.20623 [doi] PST - ppublish SO - J Orthop Res. 2008 Jul;26(7):910-7. doi: 10.1002/jor.20623.