Skip to main content
Top
Published in: International Orthopaedics 3/2012

01-03-2012 | Original Paper

Dual function of β-catenin in articular cartilage growth and degeneration at different stages of postnatal cartilage development

Authors: Bo Ning, Peng Wang, Xinghong Pei, Yingquan Kang, Jun Song, Dahui Wang, Wanglin Zhang, Ruixue Ma

Published in: International Orthopaedics | Issue 3/2012

Login to get access

Abstract

Purpose

The objective of this study was to determine the role of β-catenin in normal postnatal articular cartilage growth and degeneration.

Methods

We investigated β-catenin gene and protein expression in hip cartilage cells of normal Wistar rats at two, four, six and eight weeks of age by using reverse transcriptase polymerase chain reaction (RT-PCR) and immunohistochemistry. Primary articular chondrocytes from eight week old rats were cultured and treated with LiCl for activation of β-catenin. Collagen X and matrix metalloproteinase 13 (MMP-13) were detected by quantitative RT-PCR and immunofluorescence. A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-4 and 5 were detected by quantitative RT-PCR, and terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) was used for detecting cell apoptosis.

Results

The highest levels of β-catenin expressions were detected in two week old rats, after which a steady decline was observed over the remaining period of observation (p < 0.05). When primary articular chondrocytes from eight week old rats were treated with LiCl, β-catenin mRNA and protein were induced (p < 0.05). Moreover, LiCl-activated β-catenin in chondrocytes was associated with significant concomitant increases in mRNA expression of collagen X and the MMP-13 encoding collagenase 3. Significantly increased mRNA expression of ADAMTS-5 was also seen in primary chondrocytes from eight week old rats after LiCl treatment (p < 0.05). The effect was specific to ADAMTS-5 since ADAMTS-4, which has similar proteolytic activity but different aggrecanase activity, was unaffected. Finally, TUNEL staining revealed that LiCl-activated β-catenin signalling led to increased cell apoptotic events in chondrocytes (p < 0.05).

Conclusions

Our findings suggest that normal spatiotemporal patterns and degrees of Wnt/β-catenin signalling are needed to maintain postnatal articular cartilage growth and function. In the early stages of cartilage development, activation of β-catenin signalling is necessary for articular cartilage growth, while in adult cartilage it leads to degeneration and osteoarthritic-like chondrocytes.
Literature
1.
go back to reference Martel-Pelletier J, Boileau C, Pelletier J, Roughley P (2008) Cartilage in normal and osteoarthritis conditions. Best Pract Res Clin Rheumatol 22(2):351–384PubMedCrossRef Martel-Pelletier J, Boileau C, Pelletier J, Roughley P (2008) Cartilage in normal and osteoarthritis conditions. Best Pract Res Clin Rheumatol 22(2):351–384PubMedCrossRef
3.
go back to reference da Silva MA, Yamada N, Clarke NM, Roach HI (2009) Cellular and epigenetic features of a young healthy and a young osteoarthritic cartilage compared with aged control and OA cartilage. J Orthop Res 27(5):593–601PubMedCrossRef da Silva MA, Yamada N, Clarke NM, Roach HI (2009) Cellular and epigenetic features of a young healthy and a young osteoarthritic cartilage compared with aged control and OA cartilage. J Orthop Res 27(5):593–601PubMedCrossRef
4.
go back to reference Brandt KD, Dieppe P, Radin EL (2008) Etiopathogenesis of osteoarthritis. Rheum Dis Clin North Am 34(3):531–559PubMedCrossRef Brandt KD, Dieppe P, Radin EL (2008) Etiopathogenesis of osteoarthritis. Rheum Dis Clin North Am 34(3):531–559PubMedCrossRef
5.
go back to reference Yano F, Kugimiya F, Ohba S, Ikeda T, Chikuda H, Ogasawara T, Ogata N, Takato T, Nakamura K, Kawaguchi H (2005) The canonical Wnt signaling pathway promotes chondrocyte differentiation in a Sox9-dependent manner. Biochem Biophys Res Commun 333(4):1300–1308PubMedCrossRef Yano F, Kugimiya F, Ohba S, Ikeda T, Chikuda H, Ogasawara T, Ogata N, Takato T, Nakamura K, Kawaguchi H (2005) The canonical Wnt signaling pathway promotes chondrocyte differentiation in a Sox9-dependent manner. Biochem Biophys Res Commun 333(4):1300–1308PubMedCrossRef
6.
go back to reference Hill TP, Spater D, Taketo MM, Birchmeier W, Hartmann C (2005) Canonical Wnt/beta-catenin signaling prevents osteoblasts from differentiating into chondrocytes. Dev Cell 8(5):727–738PubMedCrossRef Hill TP, Spater D, Taketo MM, Birchmeier W, Hartmann C (2005) Canonical Wnt/beta-catenin signaling prevents osteoblasts from differentiating into chondrocytes. Dev Cell 8(5):727–738PubMedCrossRef
7.
go back to reference Yuasa T, Otani T, Koike T, Iwamoto M, Enomoto-Iwamoto M (2008) Wnt/β-catenin signaling stimulates matrix catabolic genes and activity in articular chondrocytes: its possible role in joint degeneration. Lab Invest 88(3):264–274PubMedCrossRef Yuasa T, Otani T, Koike T, Iwamoto M, Enomoto-Iwamoto M (2008) Wnt/β-catenin signaling stimulates matrix catabolic genes and activity in articular chondrocytes: its possible role in joint degeneration. Lab Invest 88(3):264–274PubMedCrossRef
8.
go back to reference Tamamura Y, Otani T, Kanatani N, Koyama E, Kitagaki J, Komori T, Yamada Y, Costantini F, Wakisaka S, Pacifici M, Iwamoto M, Enomoto-Iwamoto M (2005) Developmental regulation of Wnt/beta-catenin signals is required for growth plate assembly, cartilage integrity, and endochondral ossification. J Biol Chem 280(19):19185–19195PubMedCrossRef Tamamura Y, Otani T, Kanatani N, Koyama E, Kitagaki J, Komori T, Yamada Y, Costantini F, Wakisaka S, Pacifici M, Iwamoto M, Enomoto-Iwamoto M (2005) Developmental regulation of Wnt/beta-catenin signals is required for growth plate assembly, cartilage integrity, and endochondral ossification. J Biol Chem 280(19):19185–19195PubMedCrossRef
9.
10.
go back to reference Day TF, Guo X, Garrett-Beal L, Yang Y (2005) Wnt/beta-catenin signaling in mesenchymal progenitors controls osteoblast and chondrocyte differentiation during vertebrate skeletogenesis. Dev Cell 8(5):739–750PubMedCrossRef Day TF, Guo X, Garrett-Beal L, Yang Y (2005) Wnt/beta-catenin signaling in mesenchymal progenitors controls osteoblast and chondrocyte differentiation during vertebrate skeletogenesis. Dev Cell 8(5):739–750PubMedCrossRef
11.
go back to reference Akiyama H, Lyons JP, Mori-Akiyama Y, Yang X, Zhang R, Zhang Z, Deng JM, Taketo MM, Nakamura T, Behringer RR, McCrea PD, de Crombrugghe B (2004) Interactions between Sox9 and beta-catenin control chondrocyte differentiation. Genes Dev 18(9):1072–1087PubMedCrossRef Akiyama H, Lyons JP, Mori-Akiyama Y, Yang X, Zhang R, Zhang Z, Deng JM, Taketo MM, Nakamura T, Behringer RR, McCrea PD, de Crombrugghe B (2004) Interactions between Sox9 and beta-catenin control chondrocyte differentiation. Genes Dev 18(9):1072–1087PubMedCrossRef
12.
go back to reference Chen M, Zhu M, Awad H, Li TF, Sheu TJ, Boyce BF, Chen D, O’Keefe RJ (2008) Inhibition of beta-catenin signaling causes defects in postnatal cartilage development. J Cell Sci 121(Pt 9):1455–1465PubMedCrossRef Chen M, Zhu M, Awad H, Li TF, Sheu TJ, Boyce BF, Chen D, O’Keefe RJ (2008) Inhibition of beta-catenin signaling causes defects in postnatal cartilage development. J Cell Sci 121(Pt 9):1455–1465PubMedCrossRef
13.
go back to reference Zhu M, Tang D, Wu Q, Hao S, Chen M, Xie C, Rosier RN, O’Keefe RJ, Zuscik M, Chen D (2009) Activation of beta-catenin signaling in articular chondrocytes leads to osteoarthritis-like phenotype in adult beta-catenin conditional activation mice. J Bone Miner Res 24(1):12–21PubMedCrossRef Zhu M, Tang D, Wu Q, Hao S, Chen M, Xie C, Rosier RN, O’Keefe RJ, Zuscik M, Chen D (2009) Activation of beta-catenin signaling in articular chondrocytes leads to osteoarthritis-like phenotype in adult beta-catenin conditional activation mice. J Bone Miner Res 24(1):12–21PubMedCrossRef
14.
go back to reference Papathanasiou I, Malizos KN, Tsezou A (2010) Low-density lipoprotein receptor-related protein 5 (LRP5) expression in human osteoarthritic chondrocytes. J Orthop Res 28(3):348–353PubMed Papathanasiou I, Malizos KN, Tsezou A (2010) Low-density lipoprotein receptor-related protein 5 (LRP5) expression in human osteoarthritic chondrocytes. J Orthop Res 28(3):348–353PubMed
15.
go back to reference Blom AB, Brockbank SM, van Lent PL, van Beuningen HM, Geurts J, Takahashi N, van der Kraan PM, van de Loo FA, Schreurs BW, Clements K, Newham P, van den Berg WB (2009) Involvement of the Wnt signaling pathway in experimental and human osteoarthritis: prominent role of Wnt-induced signaling protein 1. Arthritis Rheum 60(2):501–512PubMedCrossRef Blom AB, Brockbank SM, van Lent PL, van Beuningen HM, Geurts J, Takahashi N, van der Kraan PM, van de Loo FA, Schreurs BW, Clements K, Newham P, van den Berg WB (2009) Involvement of the Wnt signaling pathway in experimental and human osteoarthritis: prominent role of Wnt-induced signaling protein 1. Arthritis Rheum 60(2):501–512PubMedCrossRef
16.
go back to reference Jones SE, Jomary C (2002) Secreted Frizzled-related proteins: searching for relationships and patterns. Bioessays 24(9):811–820PubMedCrossRef Jones SE, Jomary C (2002) Secreted Frizzled-related proteins: searching for relationships and patterns. Bioessays 24(9):811–820PubMedCrossRef
17.
go back to reference Lories RJ, Peeters J, Bakker A, Tylzanowski P, Derese I, Schrooten J, Thomas JT, Luyten FP (2007) Articular cartilage and biomechanical properties of the long bones in Frzb-knockout mice. Arthritis Rheum 56(12):4095–4103PubMedCrossRef Lories RJ, Peeters J, Bakker A, Tylzanowski P, Derese I, Schrooten J, Thomas JT, Luyten FP (2007) Articular cartilage and biomechanical properties of the long bones in Frzb-knockout mice. Arthritis Rheum 56(12):4095–4103PubMedCrossRef
18.
19.
go back to reference Li J, Khavandgar Z, Lin SH, Murshed M (2011) Lithium chloride attenuates BMP-2 signaling and inhibits osteogenic differentiation through a novel WNT/GSK3- independent mechanism. Bone 48(2):321–331PubMedCrossRef Li J, Khavandgar Z, Lin SH, Murshed M (2011) Lithium chloride attenuates BMP-2 signaling and inhibits osteogenic differentiation through a novel WNT/GSK3- independent mechanism. Bone 48(2):321–331PubMedCrossRef
20.
go back to reference Hiyama A, Sakai D, Risbud MV, Tanaka M, Arai F, Abe K, Mochida J (2010) Enhancement of intervertebral disc cell senescence by WNT/beta-catenin signaling-induced matrix metalloproteinase expression. Arthritis Rheum 62(10):3036–3047PubMedCrossRef Hiyama A, Sakai D, Risbud MV, Tanaka M, Arai F, Abe K, Mochida J (2010) Enhancement of intervertebral disc cell senescence by WNT/beta-catenin signaling-induced matrix metalloproteinase expression. Arthritis Rheum 62(10):3036–3047PubMedCrossRef
21.
go back to reference Yano F, Kugimiya F, Ohba S, Ikeda T, Chikuda H, Ogasawara T, Ogata N, Takato T, Nakamura K, Kawaguchi H, Chung UI (2005) The canonical Wnt signaling pathway promotes chondrocyte differentiation in a Sox9-dependent manner. Biochem Biophys Res Commun 333(4):1300–1308PubMedCrossRef Yano F, Kugimiya F, Ohba S, Ikeda T, Chikuda H, Ogasawara T, Ogata N, Takato T, Nakamura K, Kawaguchi H, Chung UI (2005) The canonical Wnt signaling pathway promotes chondrocyte differentiation in a Sox9-dependent manner. Biochem Biophys Res Commun 333(4):1300–1308PubMedCrossRef
22.
go back to reference Wu Q, Zhu M, Rosier RN, Zuscik MJ, O’Keefe RJ, Chen D (2010) β-catenin, cartilage, and osteoarthritis. Ann N Y Acad Sci 1192(1):344–350PubMedCrossRef Wu Q, Zhu M, Rosier RN, Zuscik MJ, O’Keefe RJ, Chen D (2010) β-catenin, cartilage, and osteoarthritis. Ann N Y Acad Sci 1192(1):344–350PubMedCrossRef
23.
go back to reference Wu Q, Huang JH, Sampson ER, Kim K-O, Zuscik MJ, O’Keefe RJ, Chen D, Rosier RN (2009) Smurf2 induces degradation of GSK-3β and upregulates β-catenin in chondrocytes: a potential mechanism for Smurf2-induced degeneration of articular cartilage. Exp Cell Res 315(14):2386–2398PubMedCrossRef Wu Q, Huang JH, Sampson ER, Kim K-O, Zuscik MJ, O’Keefe RJ, Chen D, Rosier RN (2009) Smurf2 induces degradation of GSK-3β and upregulates β-catenin in chondrocytes: a potential mechanism for Smurf2-induced degeneration of articular cartilage. Exp Cell Res 315(14):2386–2398PubMedCrossRef
24.
go back to reference Borovecki F, Pecina-Slaus N, Vukicevic S (2007) Biological mechanisms of bone and cartilage remodelling–genomic perspective. Int Orthop 31(6):799–805PubMedCrossRef Borovecki F, Pecina-Slaus N, Vukicevic S (2007) Biological mechanisms of bone and cartilage remodelling–genomic perspective. Int Orthop 31(6):799–805PubMedCrossRef
25.
go back to reference Loughlin J (2002) Genome studies and linkage in primary osteoarthritis. Rheum Dis Clin North Am 28(1):95–109PubMedCrossRef Loughlin J (2002) Genome studies and linkage in primary osteoarthritis. Rheum Dis Clin North Am 28(1):95–109PubMedCrossRef
26.
go back to reference Spector TD, MacGregor AJ (2004) Risk factors for osteoarthritis: genetics. Osteoarthritis Cartilage 12 Suppl A:S39–S44 Spector TD, MacGregor AJ (2004) Risk factors for osteoarthritis: genetics. Osteoarthritis Cartilage 12 Suppl A:S39–S44
27.
go back to reference Yuasa T, Kondo N, Yasuhara R, Shimono K, Mackem S, Pacifici M, Iwamoto M, Enomoto-Iwamoto M (2009) Transient activation of Wnt/{beta}-catenin signaling induces abnormal growth plate closure and articular cartilage thickening in postnatal mice. Am J Pathol 175(5):1993–2003PubMedCrossRef Yuasa T, Kondo N, Yasuhara R, Shimono K, Mackem S, Pacifici M, Iwamoto M, Enomoto-Iwamoto M (2009) Transient activation of Wnt/{beta}-catenin signaling induces abnormal growth plate closure and articular cartilage thickening in postnatal mice. Am J Pathol 175(5):1993–2003PubMedCrossRef
28.
go back to reference Dao DY, Yang X, Flick LM, Chen D, Hilton MJ, O’Keefe RJ (2010) Axin2 regulates chondrocyte maturation and axial skeletal development. J Orthop Res 28(1):89–95PubMed Dao DY, Yang X, Flick LM, Chen D, Hilton MJ, O’Keefe RJ (2010) Axin2 regulates chondrocyte maturation and axial skeletal development. J Orthop Res 28(1):89–95PubMed
29.
go back to reference Walker GD, Fischer M, Gannon J, Thompson RC Jr, Oegema TR Jr (1995) Expression of type-X collagen in osteoarthritis. J Orthop Res 13(1):4–12PubMedCrossRef Walker GD, Fischer M, Gannon J, Thompson RC Jr, Oegema TR Jr (1995) Expression of type-X collagen in osteoarthritis. J Orthop Res 13(1):4–12PubMedCrossRef
30.
go back to reference Cancel M, Grimard G, Thuillard-Crisinel D, Moldovan F, Villemure I (2009) Effects of in vivo static compressive loading on aggrecan and type II and X collagens in the rat growth plate extracellular matrix. Bone 44(2):306–315PubMedCrossRef Cancel M, Grimard G, Thuillard-Crisinel D, Moldovan F, Villemure I (2009) Effects of in vivo static compressive loading on aggrecan and type II and X collagens in the rat growth plate extracellular matrix. Bone 44(2):306–315PubMedCrossRef
31.
go back to reference Meyer RA Jr, Meyer MH, Ashraf N, Frick S (2007) Changes in mRNA gene expression during growth in the femoral head of the young rat. Bone 40(6):1554–1564PubMedCrossRef Meyer RA Jr, Meyer MH, Ashraf N, Frick S (2007) Changes in mRNA gene expression during growth in the femoral head of the young rat. Bone 40(6):1554–1564PubMedCrossRef
32.
go back to reference Kirsch T, Swoboda B, Nah H (2000) Activation of annexin II and V expression, terminal differentiation, mineralization and apoptosis in human osteoarthritic cartilage. Osteoarthritis Cartilage 8(4):294–302PubMedCrossRef Kirsch T, Swoboda B, Nah H (2000) Activation of annexin II and V expression, terminal differentiation, mineralization and apoptosis in human osteoarthritic cartilage. Osteoarthritis Cartilage 8(4):294–302PubMedCrossRef
33.
go back to reference Orlandi A, Oliva F, Taurisano G, Candi E, Di Lascio A, Melino G, Spagnoli LG, Tarantino U (2008) Transglutaminase-2 differently regulates cartilage destruction and osteophyte formation in a surgical model of osteoarthritis. Amino Acids 36(4):755–763PubMedCrossRef Orlandi A, Oliva F, Taurisano G, Candi E, Di Lascio A, Melino G, Spagnoli LG, Tarantino U (2008) Transglutaminase-2 differently regulates cartilage destruction and osteophyte formation in a surgical model of osteoarthritis. Amino Acids 36(4):755–763PubMedCrossRef
34.
go back to reference Moldovan F, Pelletier JP, Hambor J, Cloutier JM, Martel-Pelletier J (1997) Collagenase-3 (matrix metalloprotease 13) is preferentially localized in the deep layer of human arthritic cartilage in situ: in vitro mimicking effect by transforming growth factor beta. Arthritis Rheum 40(9):1653–1661PubMedCrossRef Moldovan F, Pelletier JP, Hambor J, Cloutier JM, Martel-Pelletier J (1997) Collagenase-3 (matrix metalloprotease 13) is preferentially localized in the deep layer of human arthritic cartilage in situ: in vitro mimicking effect by transforming growth factor beta. Arthritis Rheum 40(9):1653–1661PubMedCrossRef
35.
go back to reference Wang X, Manner PA, Horner A, Shum L, Tuan RS, Nuckolls GH (2004) Regulation of MMP-13 expression by RUNX2 and FGF2 in osteoarthritic cartilage. Osteoarthritis Cartilage 12(12):963–973PubMedCrossRef Wang X, Manner PA, Horner A, Shum L, Tuan RS, Nuckolls GH (2004) Regulation of MMP-13 expression by RUNX2 and FGF2 in osteoarthritic cartilage. Osteoarthritis Cartilage 12(12):963–973PubMedCrossRef
36.
go back to reference Plaas A, Osborn B, Yoshihara Y, Bai Y, Bloom T, Nelson F, Mikecz K, Sandy JD (2007) Aggrecanolysis in human osteoarthritis: confocal localization and biochemical characterization of ADAMTS5-hyaluronan complexes in articular cartilages. Osteoarthritis Cartilage 15(7):719–734PubMedCrossRef Plaas A, Osborn B, Yoshihara Y, Bai Y, Bloom T, Nelson F, Mikecz K, Sandy JD (2007) Aggrecanolysis in human osteoarthritis: confocal localization and biochemical characterization of ADAMTS5-hyaluronan complexes in articular cartilages. Osteoarthritis Cartilage 15(7):719–734PubMedCrossRef
37.
go back to reference 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 cartilage in vivo and in vitro. Nature 434(7033):648–652PubMedCrossRef 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 cartilage in vivo and in vitro. Nature 434(7033):648–652PubMedCrossRef
38.
go back to reference Malfait AM, Ritchie J, Gil AS, Austin JS, Hartke J, Qin W, Tortorella MD, Mogil JS (2010) ADAMTS-5 deficient mice do not develop mechanical allodynia associated with osteoarthritis following medial meniscal destabilization. Osteoarthritis Cartilage 18(4):572–580PubMedCrossRef Malfait AM, Ritchie J, Gil AS, Austin JS, Hartke J, Qin W, Tortorella MD, Mogil JS (2010) ADAMTS-5 deficient mice do not develop mechanical allodynia associated with osteoarthritis following medial meniscal destabilization. Osteoarthritis Cartilage 18(4):572–580PubMedCrossRef
39.
go back to reference 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(7033):644–648PubMedCrossRef 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(7033):644–648PubMedCrossRef
40.
go back to reference Zhong M, Carney DH, Jo H, Boyan BD, Schwartz Z (2011) Inorganic phosphate induces mammalian growth plate chondrocyte apoptosis in a mitochondrial pathway involving nitric oxide and JNK MAP kinase. Calcif Tissue Int 88(2):96–108PubMedCrossRef Zhong M, Carney DH, Jo H, Boyan BD, Schwartz Z (2011) Inorganic phosphate induces mammalian growth plate chondrocyte apoptosis in a mitochondrial pathway involving nitric oxide and JNK MAP kinase. Calcif Tissue Int 88(2):96–108PubMedCrossRef
41.
go back to reference Zhu M, Chen M, Zuscik M, Wu Q, Wang YJ, Rosier RN, O’Keefe RJ, Chen D (2008) Inhibition of beta-catenin signaling in articular chondrocytes results in articular cartilage destruction. Arthritis Rheum 58(7):2053–2064PubMedCrossRef Zhu M, Chen M, Zuscik M, Wu Q, Wang YJ, Rosier RN, O’Keefe RJ, Chen D (2008) Inhibition of beta-catenin signaling in articular chondrocytes results in articular cartilage destruction. Arthritis Rheum 58(7):2053–2064PubMedCrossRef
42.
go back to reference Guo H, Luo Q, Zhang J, Lin H, Xia L, He C (2011) Comparing different physical factors on serum TNF-alpha levels, chondrocyte apoptosis, caspase-3 and caspase-8 expression in osteoarthritis of the knee in rabbits. Joint Bone Spine. Epub ahead of print Guo H, Luo Q, Zhang J, Lin H, Xia L, He C (2011) Comparing different physical factors on serum TNF-alpha levels, chondrocyte apoptosis, caspase-3 and caspase-8 expression in osteoarthritis of the knee in rabbits. Joint Bone Spine. Epub ahead of print
Metadata
Title
Dual function of β-catenin in articular cartilage growth and degeneration at different stages of postnatal cartilage development
Authors
Bo Ning
Peng Wang
Xinghong Pei
Yingquan Kang
Jun Song
Dahui Wang
Wanglin Zhang
Ruixue Ma
Publication date
01-03-2012
Publisher
Springer-Verlag
Published in
International Orthopaedics / Issue 3/2012
Print ISSN: 0341-2695
Electronic ISSN: 1432-5195
DOI
https://doi.org/10.1007/s00264-011-1315-6

Other articles of this Issue 3/2012

International Orthopaedics 3/2012 Go to the issue