Osteoblastogenesis and Adipogenesis Are Higher in Osteoarthritic than in Osteoporotic Bone Tissue

被引:42
作者
Dragojevic, Jana [1 ]
Logar, Darja Bitenc [1 ]
Komadina, Radko [2 ]
Marc, Janja [1 ]
机构
[1] Univ Ljubljana, Fac Pharm, Dept Clin Biochem, SI-1000 Ljubljana, Slovenia
[2] Gen & Teaching Hosp Celje, Dept Traumatol, Celje, Slovenia
关键词
PPAR gamma; RUNX2; Gene expression; Fracture; Osteoporosis; Osteoarthritis; ACTIVATED RECEPTOR-GAMMA; PPAR-GAMMA; GENE-EXPRESSION; ADIPOSE-TISSUE; INVERSE RELATIONSHIP; LIPID-METABOLISM; IN-VIVO; DIFFERENTIATION; MARROW; HYPOXIA;
D O I
10.1016/j.arcmed.2011.08.005
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
100103 [病原生物学]; 100218 [急诊医学];
摘要
Background and Aims. New data show that increased adipogenesis in bone marrow may decrease osteoblastogenesis, resulting in osteoporosis (OP). Runt-related transcription factor 2 (RUNX2) and peroxisome proliferator-activated receptor gamma (PPAR gamma) are two main transcriptional regulators controlling osteoblastogenesis and adipogenesis from the same precursor cell in bone-the mesenchymal stem cell. Because osteoarthritis (OA) and OP present the opposing bone phenotype, our aim was to determine whether the expression of selected adipogenic genes is lower in OA compared to OP bone tissue. Methods. Bone samples were obtained from gender-matched OP (n = 54) and OA (n = 49) patients undergoing hip arthroplasty. Osteoblastogenesis and adipogenesis were estimated by gene expression analysis of RUNX2, PPAR gamma 2 and their downstream genes. Results. In OA bone, significantly higher expression of PPAR gamma 2 and adiponectin as well as RUNX2, osterix and osteocalcin were obtained, suggesting higher adipogenesis and osteoblastogenesis in OA than in OP. There were no differences in RUNX2/PPAR gamma 2 and osteocalcin/adiponectin ratios between groups, suggesting similar balance of both processes. Higher perilipin 2, angiopoietin-like 4 and fatty-acid binding protein 4 mRNA levels in OP suggest activation of other transcription factors or hypoxic conditions in OP bone. Conclusions. Regulation of bone formation by RUNX2 and PPAR gamma 2 is modified in OA compared to OP, resulting in higher osteoblastogenesis and adipogenesis in OA. Both processes are similarly balanced in OP and OA but less active in OP. (C) 2011 IMSS. Published by Elsevier Inc.
引用
收藏
页码:392 / 397
页数:6
相关论文
共 43 条
[1]
PPARγ insufficiency enhances osteogenesis through osteoblast formation from bone marrow progenitors [J].
Akune, T ;
Ohba, S ;
Kamekura, S ;
Yamaguchi, M ;
Chung, UI ;
Kubota, N ;
Terauchi, Y ;
Harada, Y ;
Azuma, Y ;
Nakamura, K ;
Kadowaki, T ;
Kawaguchi, H .
JOURNAL OF CLINICAL INVESTIGATION, 2004, 113 (06) :846-855
[2]
Rosiglitazone causes bone loss in mice by suppressing osteoblast differentiation and bone formation [J].
Ali, AA ;
Weinstein, RS ;
Stewart, SA ;
Parfitt, AM ;
Manolagas, SC ;
Jilka, RL .
ENDOCRINOLOGY, 2005, 146 (03) :1226-1235
[3]
Osteoarthritis: a problem of growth not decay [J].
Aspden, R. M. .
RHEUMATOLOGY, 2008, 47 (10) :1452-1460
[4]
PPARγ is required for placental, cardiac, and adipose tissue development [J].
Barak, Y ;
Nelson, MC ;
Ong, ES ;
Jones, YZ ;
Ruiz-Lozano, P ;
Chien, KR ;
Koder, A ;
Evans, RM .
MOLECULAR CELL, 1999, 4 (04) :585-595
[5]
Enhanced bone formation in lipodystrophic PPARγhyp/hyp mice relocates haematopoiesis to the spleen [J].
Cock, TA ;
Back, J ;
Elefteriou, F ;
Karsenty, G ;
Kastner, P ;
Chan, S ;
Auwerx, J .
EMBO REPORTS, 2004, 5 (10) :1007-1012
[6]
Adipose tissue expression of the lipid droplet-associating proteins S3-12 and perilipin is controlled by peroxisome proliferator-activated receptor-γ [J].
Dalen, KT ;
Schoonjans, K ;
Ulven, SM ;
Weedon-Fekjaer, MS ;
Bentzen, TG ;
Koutnikova, H ;
Auwerx, J ;
Nebbl, HI .
DIABETES, 2004, 53 (05) :1243-1252
[7]
Dequeker J, 1996, BRIT J RHEUMATOL, V35, P813
[8]
Osf2/Cbfa1: A transcriptional activator of osteoblast differentiation [J].
Ducy, P ;
Zhang, R ;
Geoffroy, V ;
Ridall, AL ;
Karsenty, G .
CELL, 1997, 89 (05) :747-754
[9]
A Cbfa1-dependent genetic pathway controls bone formation beyond embryonic development [J].
Ducy, P ;
Starbuck, M ;
Priemel, M ;
Shen, JH ;
Pinero, G ;
Geoffroy, V ;
Amling, M ;
Karsenty, G .
GENES & DEVELOPMENT, 1999, 13 (08) :1025-1036
[10]
The organization, promoter analysis, and expression of the human PPAR gamma gene [J].
Fajas, L ;
Auboeuf, D ;
Raspe, E ;
Schoonjans, K ;
Lefebvre, AM ;
Saladin, R ;
Najib, J ;
Laville, M ;
Fruchart, JC ;
Deeb, S ;
VidalPuig, A ;
Flier, J ;
Briggs, MR ;
Staels, B ;
Vidal, H ;
Auwerx, J .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (30) :18779-18789