The expression of matrix metalloproteinase-13 and osteocalcin in mouse osteoblasts is related to osteoblastic differentiation and is modulated by 1,25-dihydroxyvitamin D3 and thyroid hormones.
Matrix metalloproteinase-13 (MMP-13), is a key protein of bone matrix degradation, and is highly expressed by osteoblasts. We used the osteoblast-like MC3T3-E1 cell line and compared the stimulatory effects of the bone resorptive agents 1,25-dihydroxyvitamin D3 (1,25-(OH)(2)D(3)) 3,3',5-triido-L-thyronine (T3) on the expression of MMP-13 mRNA. We showed that the stimulatory effects were time and dose dependent, and were also transduced to the protein level, with 1,25-(OH)(2)D(3)being more potent.MMP-13 expression in different mouse cells and its localization within developing bone from the onset of osteogenesis were also investigated. 1,25-(OH)(2)D(3)- and T3-regulated osteocalcin (Osc) expression in mouse osteoblasts was compared to hormonal effects on MMP-13 expression and activity. Here we show divergent and common roles of 1,25-(OH)(2)D(3)and T3 action on the expression of these marker proteins, depending on the stage of cell differentiation. In addition, we propose a role for MMP-13 in the bone collar of developing long bones. The results could help to more precisely characterize hormonal regulation in the developmental sequence of osteoblasts.
Fratzl-Zelman
Nadja
N
Ludwig Boltzmann Institute of Osteology, 4th Medical Department, Hanusch Hospital, Heinrich Collin-Str. 30, A-1140 Vienna, Austria. fratzl@ap.univie.ac.at
Glantschnig
Helmut
H
Rumpler
Monika
M
Nader
Alexander
A
Ellinger
Adolf
A
Varga
Franz
F
D000818:Animals; D000831:Animals, Newborn; D001857:Bone Matrix / Q000187:drug effects / Q000201:enzymology; D001862:Bone Resorption / Q000139:chemically induced / Q000201:enzymology; D002117:Calcitriol / Q000378:metabolism* / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D017364:Collagenases / Q000096:biosynthesis / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D005333:Fetus; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000502:physiology; D053509:Matrix Metalloproteinase 13; D051379:Mice; D008809:Mice, Inbred C3H; D041681:NIH 3T3 Cells; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D015675:Osteocalcin / Q000378:metabolism*; D010012:Osteogenesis / Q000187:drug effects / Q000502:physiology; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D011884:Radius / Q000187:drug effects / Q000201:enzymology / Q000254:growth & development; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D012886:Skull / Q000187:drug effects / Q000201:enzymology / Q000254:growth & development; D014284:Triiodothyronine / Q000378:metabolism* / Q000494:pharmacology; D014457:Ulna / Q000187:drug effects / Q000201:enzymology / Q000254:growth & development
D012333:RNA, Messenger; D014284:Triiodothyronine; D015675:Osteocalcin; D017364:Collagenases; D053509:Matrix Metalloproteinase 13; C507081:Mmp13 protein, mouse; D002117:Calcitriol