PMID- 10646116
OWN - NLM
STAT- MEDLINE
DCOM- 20000211
LR  - 20161124
IS  - 0884-0431 (Print)
IS  - 0884-0431 (Linking)
VI  - 15
IP  - 1
DP  - 2000 Jan
TI  - Role of the latent transforming growth factor beta binding protein 1 in
      fibrillin-containing microfibrils in bone cells in vitro and in vivo.
PG  - 68-81
AB  - Latent transforming growth factor beta-binding proteins (LTBPs) are extracellular
      matrix (ECM) proteins that bind latent transforming growth factor beta (TGF-beta)
      and influence its availability in bone and other connective tissues. LTBPs have
      homology with fibrillins and may have related functions as microfibrillar
      proteins. However, at present little is known about their structural arrangement 
      in the ECM. By using antibodies against purified LTBP1, against a short peptide
      in LTBP1, and against epitope-tagged LTBP1 constructs, we have shown
      colocalization of LTBP1 and fibrillin 1 in microfibrillar structures in the ECM
      of cultured primary osteoblasts. Immunoelectron microscopy confirmed localization
      of LTBP1 to 10- to 12-nm microfibrils and suggested an ordered aggregation of
      LTBP1 into these structures. Early colocalization of LTBP1 with fibronectin
      suggested a role for fibronectin in the initial assembly of LTBP1 into the
      matrix; however, in more differentiated osteoblast cultures, LTBP1 and
      fibronectin 1 were found in distinct fibrillar networks. Overexpression of LTBP1 
      deletion constructs in osteoblast-like cells showed that N-terminal amino acids
      67-467 were sufficient for incorporation into fibrillin-containing microfibrils
      and suggested that LTBP1 can be produced by cells distant from the site of fibril
      formation. In embryonic long bones in vivo, LTBP1 and fibrillin 1 colocalized at 
      the surface of newly forming osteoid and bone. However, LTBP1-positive fibrils,
      which did not contain fibrillin 1, were present in cartilage matrix. These
      studies show that in addition to regulating TGF beta 1, LTBP1 may function as a
      structural component of connective tissue microfibrils. LTBP1 may therefore be a 
      candidate gene for Marfan-related connective tissue disorders in which linkage to
      fibrillins has been excluded.
FAU - Dallas, S L
AU  - Dallas SL
AD  - Department of Medicine, University of Texas Health Science Center at San Antonio,
      USA.
FAU - Keene, D R
AU  - Keene DR
FAU - Bruder, S P
AU  - Bruder SP
FAU - Saharinen, J
AU  - Saharinen J
FAU - Sakai, L Y
AU  - Sakai LY
FAU - Mundy, G R
AU  - Mundy GR
FAU - Bonewald, L F
AU  - Bonewald LF
LA  - eng
GR  - R01AR43775/AR/NIAMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Bone Miner Res
JT  - Journal of bone and mineral research : the official journal of the American
      Society for Bone and Mineral Research
JID - 8610640
RN  - 0 (Carrier Proteins)
RN  - 0 (FBN1 protein, human)
RN  - 0 (Fibrillin-1)
RN  - 0 (Fibrillins)
RN  - 0 (Fibronectins)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (LTBP1 protein, human)
RN  - 0 (Latent TGF-beta Binding Proteins)
RN  - 0 (Microfilament Proteins)
RN  - 9007-34-5 (Collagen)
SB  - IM
MH  - Amino Acid Sequence
MH  - Blotting, Western
MH  - Bone and Bones/*metabolism/ultrastructure
MH  - Carrier Proteins/*physiology
MH  - Cell Line
MH  - Collagen/metabolism
MH  - Fibrillin-1
MH  - Fibrillins
MH  - Fibronectins/metabolism
MH  - Fluorescent Antibody Technique
MH  - Humans
MH  - *Intracellular Signaling Peptides and Proteins
MH  - Latent TGF-beta Binding Proteins
MH  - Microfibrils/*metabolism
MH  - Microfilament Proteins/*metabolism
MH  - Microscopy, Immunoelectron
MH  - Molecular Sequence Data
EDAT- 2000/01/26 09:00
MHDA- 2000/02/19 09:00
CRDT- 2000/01/26 09:00
PHST- 2000/01/26 09:00 [pubmed]
PHST- 2000/02/19 09:00 [medline]
PHST- 2000/01/26 09:00 [entrez]
AID - 10.1359/jbmr.2000.15.1.68 [doi]
PST - ppublish
SO  - J Bone Miner Res. 2000 Jan;15(1):68-81. doi: 10.1359/jbmr.2000.15.1.68.