Cell News 3/2013
20
RESEARCH NEWS
Thus, further studies on the structure and assembly of the carti-
lage ECM under physiological pathogenic conditions will provide
significant insight into disease mechanisms and help to identify
therapeutic targets for the treatment of cartilage diseases.
References
Aszodi A, Chan D, Hunziker E, Bateman JF, Fässler R. 1998. Collagen II is essential for the re-
moval of the notochord and the formation of intervertebral discs. J Cell Biol 143: 1399-1412
Bell PA, Wagener R, Zaucke F, Koch M, Selley J, Warwood S, Knight D, Boot-Handford RP,
Thornton DJ, Briggs MD. 2013. Analysis of the cartilage proteome from three different mouse
models of genetic skeletal diseases reveals common and discrete disease signatures. Biol
Open 2: 802-811
Blumbach K, Bastiaansen-Jenniskens YM, DeGroot J, Paulsson M, Van Osch GVJM, Zaucke F.
2009. Combined role of collagen IX and COMP in cartilage matrix assembly - COMP coun-
teracts collagen IX limitation of cartilage collagen fibril growth. Arthritis Rheum 60: 3676-
3685
Blumbach K, Niehoff A, Paulsson M, Zaucke F. 2008. Ablation of collagen IX and COMP
disrupts epiphyseal cartilage architecture. Matrix Biol 27: 306-318
Bönnemann CG, Cox GF, Shapiro F, Wu JJ, Feener CA, Thompson TG, Anthony DC, Eyre DR,
Darras BT, Kunkel LM. 2000. A mutation in the alpha 3 chain of type IX collagen causes
autosomal dominant multiple epiphyseal dysplasia with mild myopathy. Proc Natl Acad Sci
USA 97: 1212-1217
Briggs MD, Hoffman SM, King LM, Olsen AS, Mohrenweiser H, Leroy JG, Mortier GR, Rimoin
DL, Lachman RS, Gaines ES, Cekleniak JA, Knowlton RG, Cohn DH. 1995. Pseudoachondro-
plasia and multiple epiphyseal dysplasia due to mutations in the cartilage oligomeric matrix
protein gene. Nat Genet 10: 330-336
Bruckner P. 2010. Suprastructures of extracellular matrices: paradigms of functions cont-
rolled by aggregates rather than molecules. Cell Tissue Res 339:7-18
Budde B, Blumbach K, Ylöstalo J, Zaucke F, Ehlen HWA, Wagener R, Ala-Kokko L, Paulsson
M, Bruckner P, Grässel S. 2005. Altered integration of matrilin-3 into cartilage extracellular
matrix in the absence of collagen IX. Mol Cell Biol 25: 10465-10478
Chen FH, Herndon ME, Patel N, Hecht JT, Tuan RS, Lawler J. 2007. Interaction of cartilage
oligomeric matrix protein/thrombospondin 5 with aggrecan. J Biol Chem 282: 24591-24598
Cotterill SL, Jackson GC, Leighton MP, Wagener R, Mäkitie O, Cole WG, Briggs MD. 2005.
Multiple epiphyseal dysplasia mutations in MATN3 cause misfolding of the A-domain and
prevent secretion of mutant matrilin-3. Hum Mutat 26: 557-565
Coustry F, Posey KL, Liu P, Alcorn JL, Hecht JT. 2012. D469del-COMP retention in chondrocy-
tes stimulates caspase-independent necroptosis. Am J Pathol. 180:738-748.
Dinser R, Zaucke F, Kreppel F, Hultenby K, Kochanek S, Paulsson M, Maurer P. 2002. Pseudo-
achondroplasia is caused through both intra- and extracellular pathogenic pathways. J Clin
Invest 110: 505-513
Dreier R, Opolka A, Grifka J, Bruckner P, Grassel S. 2008. Collagen IX-deficiency seriously
compromises growth cartilage development in mice. Matrix Biol 27:319-329
Fässler R, Schnegelsberg PN, Dausman J, Shinya T, Muragaki Y, McCarthy MT, Olsen BR,
Jaenisch R. 1994. Mice lacking alpha 1 (IX) collagen develop noninflammatory degenerative
joint disease. Proc Natl Acad Sci USA 91: 5070–5074
Glasson SS, Askew R, Sheppard B, Carito B, Blanchet T, Ma HL, Flannery CR, Peluso D, Kanki
K, Yang Z, Majumdar MK, Morris EA. 2005. Deletion of active ADAMTS5 prevents cartilage
degradation in a murine model of osteoarthritis. Nature 434: 644-648
Groma G, Xin W, Grskovic I, Niehoff A, Paulsson M, Brachvogel B, Zaucke F. 2012. Abnormal
bone quality in COMP and matrilin-3 double deficient mice caused by increased TIMP-3
deposition and delayed aggrecan degradation. Arthritis Rheum 64: 2644-2654
Hagg R, BrucknerP, Hedbom E. 1998. Cartilage fibrils of mammals are biochemically he-
terogeneous: differential distribution of decorin and collagen IX. J Cell Biol 142: 285-294
Halasz K, Kassner A, Morgelin M, Heinegard D. 2007. COMP acts as a catalyst in collagen
fibrillogenesis. J Biol Chem 282: 31166-31173
Hansen U, Platz N, Becker A, Bruckner P, Paulsson M, Zaucke F. 2011. A secreted variant of
cartilage oligomeric matrix protein (COMP) carrying a chondrodysplasia-causing mutation
(p.H587R) disrupts collagen fibrillogenesis. Arthritis Rheum 63: 159-167
Hashimoto Y, Tomiyama T, Yamano Y, Mori H. 2003. Mutation (D472Y) in the type 3 repeat
domain of cartilage oligomeric matrix protein affects its early vesicle trafficking in endoplas-
mic reticulum and induces apoptosis. Am J Pathol 163: 101-110
Hauser N, Paulsson M, Heinegard D, Mörgelin M. 1996. Interaction of cartilage matrix pro-
tein with aggrecan. Increased covalent cross-linking with tissue maturation. J Biol Chem
271:32247-32252
Hecht JT, Hayes E, Haynes R, Cole WG. 2005. COMP mutations, chondrocyte function and
cartilage matrix. Matrix Biol 23: 525-533
Hecht JT, Makitie O, Hayes E, Haynes R, Susic M, Montufar-Solis D, Duke PJ, Cole WG. 2004.
Chondrocyte cell death and intracellular distribution of COMP and type IX collagen in the
pseudoachondroplasia growth plate. J Orthop Res 22: 759-767
Hecht JT, Nelson LD, Crowder E, Wang Y, Elder FF, Harrison WR, Francomano CA, Prange CK,
Lennon GG, Deere M, Lawler J. 1995. Mutations in exon 17B of cartilage oligomeric matrix
protein (COMP) cause pseudoachondroplasia. Nat Genet 10: 325-329
Heinegård D, Saxne T. 2011. The role of the cartilage matrix in osteoarthritis. Nat Rev Rheu-
matol 7: 50-56
Kalamajski S, Oldberg A. 2010. The role of small leucine-rich proteoglycans in collagen fibril-
logenesis. Matrix Biol 29): 248-253
Klatt AR, Becker AK, Neacsu CD, Paulsson M, Wagener R. 2011. The matrilins: modulators of
extracellular matrix assembly. Int J Biochem Cell Biol 43: 320-330
Klatt AR, Klinger G, Paul-Klausch B, Kühn G, Renno JH, Wagener R, Paulsson M, Schmidt J,
Malchau G, Wielckens K. 2009a Matrilin-3 activates the expression of osteoarthritis-associ-
ated genes in primary human chondrocytes. FEBS Lett 583: 3611-3617
Klatt AR, Paul-Klausch B, Klinger G, Kühn G, Renno JH, Banerjee M, Malchau G, Wielckens K.
2009b. A critical role for collagen II in cartilage matrix degradation: collagen II induces pro-
inflammatory cytokines and MMPs in primary human chondrocytes. J Orthop Res 27: 65-70
Ko Y, Kobbe B, Nicolae C, Miosge N, Paulsson M, Wagener R, Aszodi A. 2004.Matrilin 3 is
dispensable for mouse skeletal growth and development. Mol Cell Biol 24: 1691-1699
Leighton MP, Nundlall S, Starborg T, Meadows RS, Suleman F, Knowles L, Wagener R, Thorn-
ton DJ, Kadler KE, Boot-Handford RP, Briggs MD. 2007. Decreased chondrocyte proliferation
and dysregulated apoptosis in the cartilage growth plate are key features of a murine model
of epiphyseal dysplasia caused by a matn3 mutation. Hum Mol Genet 16: 1728-1741
Li Y, Lacerda DA, Warman ML, Beier DR, Yoshioka H, Ninomiya Y, Oxford JT, Morris NP, An-
drikopoulos K, Ramirez F, Wardell BB, Lifferth GD, Teuscher C, Woodward SR, Taylor BA,
Seegmiller RE, Olsen BR. 1995. A fibrillar collagen gene, Col11a1, is essential for skeletal
morphogenesis. Cell 80: 423-430
Maddox BK, Keene DR, Sakai LY, Charbonneau NL, Morris NP, Ridgeway CC, Boswell BA, Suss-
man MD, Horton WA, Bächinger HP, Hecht JT. 1997. The fate of cartilage oligomeric matrix
protein is determined by the cell type in the case of a novel mutation in pseudoachondropla-
sia. J Biol Chem 272: 30993-30997
Mann HH, Özbek S, Engel J, Paulsson M, Wagener R. 2004. Interactions between COMP and
matrilins. Implications for matrix assembly and the pathogenesis of chondrodysplasias. J Biol
Chem 279: 25294-25298
Merritt TM, Bick R, Poindexter BJ, Alcorn JL, Hecht JT. 2007. Unique matrix structure in the
rough endoplasmic reticulum cisternae of pseudoachondroplasia chondrocytes. Am J Pathol
170: 293-300
Mobasheri A. 2012. Osteoarthritis year 2012 in review: biomarkers. Osteoarthritis Cartilage
20: 1451-1464
Nicolae C, Ko Y-P, Miosge N, Niehoff A, Studer D, Enggist L, Hunziker EB, Paulsson M, Wage-
ner R, Aszodi A. 2007. Abnormal collagen fibrils in cartilage of matrilin-1/matrilin-3-defici-
ent mice. J Biol Chem 282: 22163-22175
Nundlall S, Rajpar MH, Bell PA, Clowes C, Zeeff LA, Gardner B, Thornton DJ, Boot-Handford
RP, Briggs MD. 2010. An unfolded protein response is the initial cellular response to the
expression of mutant matrilin-3 in a mouse model of multiple epiphyseal dysplasia. Cell
Stress Chaperones 15: 835-849
Opolka A, Ratzinger S, Schubert T, Spiegel HU, Grifka J, Bruckner P, Probst A, Grassel S. 2007.
Collagen IX is indispensable for timely maturation of cartilage during fracture repair in mice.
Matrix Biol 26: 85-95
Otten C, Hansen U, Talke A, Wagener R, Paulsson M, Zaucke F. 2010. A matrilin-3 mutation
associated with osteoarthritis does not affect collagen affinity but promotes the formation
of wider cartilage collagen fibrils. Human Mutat 31: 254-263
Pihlajamaa T, Lankinen H, Ylöstalo J, Valmu L, Jäälinoja J, Zaucke F, Spitznagel L, Gösling
S, Puustinen A, Mörgelin M, Peränen J, Maurer P, Ala-Kokko L, Kilpeläinen I. 2004. Charac-
terization of recombinant amino-terminal NC4 domain of human collagen IX Interaction
with glycosaminoglycans and cartilage oligomeric matrix protein (COMP). J Biol Chem 279:
24265-24273
Pirog-Garcia KA, Meadows RS, Knowles L, Heinegard D, Thornton DJ, Kadler KE, Boot-Hand-
ford RP, Briggs MD. 2007. Reduced cell proliferation and increased apoptosis are significant
pathological mechanisms in a murine model of mild pseudoachondroplasia resulting from a
mutation in the C-terminal domain of COMP. Hum Mol Genet 16: 2072-2088
Posey KL, Veerisetty AC, Liu P, Wang HR, Poindexter BJ, Bick R, Alcorn JL, Hecht JT. 2009. An
inducible cartilage oligomeric matrix protein mouse model recapitulates human pseudo-
achondroplasia phenotype. Am J Pathol 175: 1555-1563
Rosenberg K, Olsson H, Morgelin M, Heinegard D. 1998. Cartilage oligomeric matrix protein
shows high affinity zinc-dependent interaction with triple helical collagen. J Biol Chem 273:
20397-20403
Schmitz M, Becker A, Schmitz A, Paulsson M, Zaucke F, Dinser R. 2006. Disruption of ext-
racellular matrix structure may cause pseudoachondroplasia phenotypes in the absence of
impaired COMP secretion. J Biol Chem 281: 32587-32595
Schmitz M, Niehoff A, Miosge N, Smyth N, Paulsson M and Zaucke F. 2008. Transgenic mice
expressing D469
Δ
mutated cartilage oligomeric matrix protein (COMP) show mild skeletal
abnormalities, sternal malformations and premature ossification. Matrix Biol 27: 67-85
Spitznagel L, Nitsche DP, Paulsson M, Maurer, P, Zaucke F. 2004. Characterization of a pseu-
doachondroplasia-associated mutation (H587R) in the carboxy-terminal, collagen-binding
domain of cartilage oligomeric matrix protein (COMP). Biochem. J.; 377: 479-487
Stanescu R, Stanescu V, Muriel MP, Maroteaux P. 1993. Multiple epiphyseal dysplasia, Fair-
bank type: morphologic and biochemical study of cartilage. Am J Med Genet 45: 501-507
Stanton H, Rogerson FM, East CJ, Golub SB, Lawlor KE, Meeker CT, Little CB, Last K, Farmer
PJ, Campbell IK, Fourie AM, Fosang AJ. 2005. ADAMTS5 is the major aggrecanase in mouse
