3+ 4/2002 - Společnost pro pojivové tkáně

and for the associated tertiary and quaternary
changes.The localization of the ligandbinding
site allows modelling of other heterodimeric
integrins bound to physiologic
ligands. It also suggests that αA, when present,
serves as an endogenous integrin ligand.
This tantalizing hypothesis, for which
supportive biochemical data exists, suggests
a unifying principle for ligand recognition
and signalling applicable in all integrins.
References: Xiong, J-P., et al. (2001)
Science 294:339-345. Xiong, J-P., et al.
(2002) Science 296:151-155.
Alonso, J., et al. (2002) Current Biology
12:R340-342
SECRETION AND MATURATION OF
BONE MORPHOGENETIC PROTEIN-1
(BMP-1).
M. P. Leiehton and K. E. Kadler.
Wellcome Trust Centre for Cell-Matrix Research, School
of Biological Sciences, 2.205 Stopford Building, University
of Manchester, Manchester, M 13 9PT UK.
Introduction: The coordination of the
initial interactions and processing events of
fibril formation is critical to the final structure
and function of fibrils. A key event of
fibril formation is the removal of the Cpropeptides
of collagen types I-III by BMP-
1.The role of BMP-1 in fibrillogenesis is critical,
playing a key role in the coordinated
activation/maturation of essential steps in
the deposition of fibrils. BMP-1 is synthesised
as a latent (inactive) molecule. Identification
of the site of maturation of BMP-
Igives an insight into the initial interactions
of fibril formation.
Methods: The potential furin cleavage
site of wild-type latent BMP-1 was mutated
to abrogate maturation (RSRR – RSAA).
Both wild-type and mutant BMP-1 had a C-
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LOCOMOTOR SYSTEM vol. 9, 2002, No. 3+4
terminal flag-tag attached (BF and BFfrespectively).
The secretion and localisation
of the proteins in HT-1080 cells was
examined using biochemical and fluorescent
microscopy analysis.
Results: Mature BF was observed in the
cell media only and latent was observed in
the cell lysate only. No mature was
observed in the cell lysate. No maturation
of BF-f was observed. BFA and monensin
abrogated maturation and secretion of BF.
Addition of furin inhibitor completely abrogated
BF maturation and led to secretion of
the Iatent form. Secreted BF (mature) was
active, while secreted latent BF and BFfwere
not active. rFurin cleaved fatent BF,
but not BF-f. BF co-localised with furin.
Discussion: BMP-1 is activated by
furin. The maturation of BF occurs prior to
secretion i.e. from the TGN to the PM. Maturation
is dependent on the furin cleavage
site. Co-localisation of BF and BF-f witli furin
is not dependent on the furin cleavage site.
FUNDAMENTAL PRIMARY BONE
REMODELLING IN OSTEOARTHRITIS-
EVIDENCE FROM THE GUINEA PIG
MODEL
J. M. Anderson-MacKenzie, H. L. Quasnichka, R. Starr,
E. J. Lewis, M. E. J. Billingham and A. J. Bailey
Collagen Research Group, Bristol University, Bristol
BS4O 7DY UK
Introduction: The role of bone change
in OA has been controversial,in this study we
compared radiographic bone density and
bone shape of the Dunkin Hartley (DH)
guinea pig, which develops OA and Bristol
Strain 2 (BS2), the non-OA developing control.
Methods: Four Male DH and four BS2
were studied at 3, 6, 9, 12, 16, 20, 24 and 36
weeks of age. Posterior-anterior (PA) and