1/2001 - Společnost pro pojivové tkáně

that modulate ECM. Isolated Drosophila papilin was incomplete degradation of the GAG chains, or
shown to inhibit such a metalloproteinase. alternatively, that proMMP-9 is covalently linked to
Overexpression of papilin is lethal in Drosophila different PG core proteins. The lack of TIMP-1 bound
embryos. We propose that papilins, themselves early to the purified proMMP-9/CSPG complexes indicates
components of ECM, influence developmental that the covalent interaction between the CSPG core
modulation of ECM.
protein and proMMP-9 prevents binding to TIMP-1 or
The evolutionarily conserved polypeptide chains that TIMP-1 was lost during the harsh puriňcation
of Peroxidasin combine several ECM domains with a procedure. As small CSPGs such as serglycin can bind
myeloperoxidase-like enzymatic domain. Isolated to the cell receptor CD44, it can be assumed that the
Drosophila peroxidasin is a heme-containing, proven CSPG molecule links MMP-9 to cell surfaces. This
peroxidase. Although we have yet to isolate the may have implications for cell motility and invasion,
corresponding vertebrate proteins, in situ factors of major importance both in normal
hybridization of neonatal mouse sections shows a remodelling events as well as in pathological
wide distribution of peroxidasin mRNA in mouse conditions such as tumor growth and metastasis.
connective tissues.
We are grateful for the fnancial support from The
Vertebrate inner ear sense organs share Norwegian Cancer Society, The Erna & Olav Aakre
histological and molecular-developmental similarities Foundation and The Norwegian Research Council.
with Drosophila vibration/stretch receptors called
chordotonal organs. Study of ECM formation during
chordotonal organ development, in whole embryos R O L E O F C AT H E P S I N K I N B O N E
and in cell cultures, revealed differential deposition of TURNOVER
ECM in microscopically circumscribed patterns. This Juho Rantakokko, Riku Kiviranta, Jukka Morko,
shows that ECM can be made and patterned by Hannele Uusitalo and Eero Vuorio
individual cells, in contradistinction to its usual Department of Medical Biochemistry and Molecular
production by groups of cells in a tissue layer. Biology, University of Turku, FIN-20520 Turku,
(Supported by NIH GM-57689).
Finland.
Several lines of evidence suggest that cathepsin
K, a cysteine proteinase produced predominantly by
M A C R O P H A G E S S E C R E T E M AT R I X osteoclasts, plays an important role in bone resorption
METALLOPROTEINASE 9 COVALENTLY and remodeling. To study the role of cathepsin K in
LINKED TO THE CORE PROTEIN OF these processes we have determined the cDNA and
C H O N D R O I T I N S U L F A T E genomic structure of the murine cathepsin K. The Ctsk
PROTEOGLYCANS.
gene spans 10.1 kb, contains 8 exons, and is located
1 1 2
Jan-Olof Winberg , Eli Berg , Svein O. Kolset and 4.5 kb downstream of the Arnt gene on mouse
Lars Uhlin-Hansen l chromosome 3 at locus 47.9. Hybridization analyses
Department of Biochemistry, Institute of Medical confirmed the predominant localization of cathepsin
Biology, University of Tromso, 9037 Tromso, Norway K mRNA in osteoclasts although small amounts were
2
and Institute of Nutrition Research, University of also identified in hypertrophying chondrocytes. Two
Oslo, Norway.
kinds of experiments have been performed to
The present work shows that under serum free determine the role of cathepsin K in bone turnover and
conditions, the leukemic macrophage cell line THP1 development of osteopenia. In a mouse disuse
produces chondroitin sulfate proteoglycans (CSPG), osteopenia model, the mRNA levels for cathepsin K
pro-matrix metalloproteinase 9 (proMMP-9) and increased in parallel with the development of
tissue inhibitor 1 of MMPs (TIMP-1). ProMMP-9 was significant osteopenia within 10-21 1 days of
detected as a monomer with a Mr of 92 kDa, as a immobilization which was detectable by
homodimer with a Mr of approximately 225 kDa, as histomorphometric, biomechanical and tomographic
well as a heterodimer, in which proMMP-9 was (pQCT) analyses. The balance of bone turnover was
covalently linked to the core protein of CSPG. It was further shifted towards net bone loss as the mRNA
shown that proMMP-9 was linked to the core protein levels for major bone components (type I collagen and
of CSPG through one or more disulfide bridges. CS osteocalcin) were concommitantly decreased. As an
depleated PG due to chondroitin ABC lyase treatment, alternative way to study the role oř cathepsin K in the
resulted in 145,127 and 109 kDa heterodimers of development of osteopenia we have produced
MMP-9/CSPG core protein, based on zymography transgenic mice harboring additional copies of the
and western blots. This heterogeneity might be due to Ctsk gene. The expression of the transgenes has
46 LOCOMOTOR SYSTEM VOL. 8, 2001, No. 1