Transforming growth factor beta2 inhibits adipocyte differentiation induced by skeletal unloading in rat bone marrow stroma.
Skeletal unloading induced by hindlimb suspension in rats reduces bone formation and induces osteopenia, but its effect on adipogenesis is unknown. We assessed the effects of unloading and transforming growth factor (TGF) beta2 on bone marrow stromal cell adipocyte differentiation in relation with osteoblast differentiation. Skeletal unloading rapidly (4-7 days) decreased osteoblast transcription factor Runx2, osteocalcin (OC), and type I collagen messenger RNA (mRNA) levels and reduced bone formation in the long bone metaphysis. Conversely, unloading increased expression of the adipocyte transcription factor peroxisome proliferator-activated receptor gamma2 (PPARgamma2) at 4 days and increased expression of the adipocyte differentiation genes lipoprotein lipase (LPL) and aP2 in the bone marrow stroma at 7 days. Consistently, unloading increased the number and volume of adipocytes in the bone marrow stroma. Continuous (0-7 days) and late (4-7 days) treatments with TGF-beta2 corrected the abnormal expression of Cbfa1/Runx2, OC, and type I collagen mRNAs and normalized bone formation in unloaded metaphyseal bone. Moreover, both TGF-beta2 treatments decreased PPARy2 and C/EBPalpha mRNA levels at 4 days and normalized aP2 and LPL expression and adipocyte number and volume at 7 days. These results show that skeletal unloading increases adipocyte differentiation concomitantly with inhibition of osteoblast differentiation. These abnormalities are prevented and reversed by TGF-beta2, suggesting a role for TGF-beta in the control of adipogenic differentiation in the bone marrow stroma.
Ahdjoudj
Souhila
S
Unit 349 INSERM, CNRS, Laboratory of Osteoblast Biology and Pathology, Lariboisière Hospital, Paris, France.
Lasmoles
Françoise
F
Holy
Xavier
X
Zerath
Erik
E
Marie
Pierre J
PJ
D017667:Adipocytes / Q000166:cytology* / Q000187:drug effects; D000818:Animals; D001846:Bone Development / Q000187:drug effects; D001853:Bone Marrow / Q000187:drug effects*; D001854:Bone Marrow Cells / Q000187:drug effects; D022762:CCAAT-Enhancer-Binding Proteins / Q000187:drug effects / Q000235:genetics; D002352:Carrier Proteins / Q000187:drug effects / Q000235:genetics; D002454:Cell Differentiation / Q000187:drug effects*; D024042:Collagen Type I / Q000187:drug effects / Q000235:genetics; D050659:Core Binding Factor Alpha 1 Subunit; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D005786:Gene Expression Regulation / Q000187:drug effects; D008071:Lipoprotein Lipase / Q000187:drug effects / Q000235:genetics; D008297:Male; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D010006:Osteoblasts / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D015675:Osteocalcin / Q000187:drug effects / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D018160:Receptors, Cytoplasmic and Nuclear / Q000187:drug effects / Q000235:genetics; D013314:Stress, Mechanical; D017154:Stromal Cells / Q000187:drug effects; D014157:Transcription Factors / Q000187:drug effects / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D053781:Transforming Growth Factor beta2; D016474:Weight-Bearing / Q000502:physiology*
D022762:CCAAT-Enhancer-Binding Proteins; D002352:Carrier Proteins; D024042:Collagen Type I; D050659:Core Binding Factor Alpha 1 Subunit; C490174:Fabp7 protein, rat; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D053781:Transforming Growth Factor beta2; D015675:Osteocalcin; D008071:Lipoprotein Lipase