m-Calpain in Rat Growth Plate Chondrocyte Cultures: Its Involvement in the Matrix Mineralization Process

Yasuda, Tadashi; Shimizu, Katsuji; Nakagawa, Yasuaki; Yamamoto, Shingo; Niibayashi, Hiroshi; Yamamuro, Takao

doi:10.1006/dbio.1995.1204

Cited by 24 publications

(11 citation statements)

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“…The calcium-dependent cysteine proteinase m-calpain also cleaves aggrecan in vitro (49,60), and fragments consistent with m-calpain cleavage are present in extracts of mature bo- vine cartilage (49). m-Calpain is a cytosolic enzyme thought to have a role in matrix mineralization (81), and it is unclear how this intracellular enzyme is able to degrade extracellular aggrecan. Whether m-calpain is involved in growth plate aggrecanolysis in vivo has not been investigated.…”

Section: Discussionmentioning

confidence: 99%

Matrix Metalloproteinases Are Not Essential for Aggrecan Turnover during Normal Skeletal Growth and Development

Little

Meeker

Hembry

et al. 2005

Molecular and Cellular Biology

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The growth plate is a transitional region of cartilage and highly diversified chondrocytes that controls long bone formation. The composition of growth plate cartilage changes markedly from the epiphysis to the metaphysis, notably with the loss of type II collagen, concomitant with an increase in MMP-13; type X collagen; and the C-propeptide of type II collagen. In contrast, the fate of aggrecan in the growth plate is not clear: there is biosynthesis and loss of aggrecan from hypertrophic cartilage, but the mechanism of loss is unknown. All matrix metalloproteinases (MMPs) cleave aggrecan between amino acids N 341 and F 342 in the proteinase-sensitive interglobular domain (IGD), and MMPs in the growth plate are thought to have a role in aggrecanolysis. We have generated mice with aggrecan resistant to proteolysis by MMPs in the IGD and found that the mice develop normally with no skeletal deformities. The mutant mice do not accumulate aggrecan, and there is no significant compensatory proteolysis occurring at alternate sites in the IGD. Our studies reveal that MMP cleavage in this key region is not a predominant mechanism for removing aggrecan from growth plate cartilage.Endochondral ossification is the process by which bone is formed upon a cartilage template. It occurs in skeletal development, in fracture healing, and during bone growth at the growth plates and involves the transition from avascular cartilage, rich in type II collagen and aggrecan, to highly vascular bone, rich in type I collagen and mineral. During endochondral bone formation, prechondrogenic mesenchymal cells differentiate into chondrocytes, which proliferate and then mature into hypertrophic chondrocytes. The hypertrophic cartilage begins to calcify, the cartilage matrix is degraded and is invaded by blood vessels, the terminal hypertrophic chondrocytes apoptose, and bone matrix is deposited on the calcified cartilage trabeculae. This is a busy schedule of events in the growth plate, and their precise timing in relation to each other has not been clearly defined.The growth plate is a striking remodeling unit both anatomically and biochemically. Anatomically, it is bordered by the secondary center of ossification and epiphysis at one end and the bony metaphysis at the other. It comprises reserve, proliferative, prehypertrophic, and hypertrophic zones. Chondrocytes in the reserve zone are rounded and sparsely distributed, whereas chondrocytes in the proliferative zone are flattened and occupy approximately one-quarter of the tissue volume. Cells of the proliferative zone divide and arrange themselves into ordered columns separated by longitudinal septa. At the same time, they increase their secretion of matrix molecules so that around 75% of the tissue volume is cartilage matrix. In the hypertrophic zones, the cells retain their columnar organization and increase their metabolic activity. They enlarge by as much as 10-fold (28) so that matrix volume is reduced to approximately 40%, with cells occupying 60% of the tissue volume (5). Calcificat...

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Section: Discussionmentioning

confidence: 99%

Matrix Metalloproteinases Are Not Essential for Aggrecan Turnover during Normal Skeletal Growth and Development

Little

Meeker

Hembry

et al. 2005

Molecular and Cellular Biology

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“…However, these studies have not specifically targeted calpain 10. Finally, calpains have been implicated in influencing signaling pathways that control differentiation of myoblasts (32), osteoblasts (33), chondrocytes (34), and preadipocytes to adipocytes (35). It is therefore clear that work should now be directed at understanding the biology of calpain10.…”

Section: Discussionmentioning

confidence: 99%

Haplotype Combinations of Calpain 10 Gene Polymorphisms Associate With Increased Risk of Impaired Glucose Tolerance and Type 2 Diabetes in South Indians

et al. 2002

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Haplotype combination 112/121 and its intrinsic variants (UCSNP43, -19, and -63) identified within the calpain 10 gene are associated with increased risk of type 2 diabetes in Mexican-Americans. We evaluated whether this haplotype combination and its constituent haplotypes and variants contribute to increased susceptibility to impaired fasting glucose (IFG)/impaired glucose tolerance (IGT) and type 2 diabetes in a South Indian population. Two study groups were used: 95 families ascertained through a proband with type 2 diabetes and 468 subjects recruited as part of an urban survey (69.1% with normal glucose tolerance, 12.8% with IFG/IGT, and 18.2% with type 2 diabetes). The four-locus haplotype combination 1112/1121 (UCSNP44, -43, -19, and -63) in South Indians conferred both a 10.7-fold increased risk for IFG/IGT (P ‫؍‬ 0.001) and a 5.78-to 6.52-fold increased risk for type 2 diabetes in the two study groups (families P ‫؍‬ 0.025, urban survey P ‫؍‬ 0.015). A combination of the 1112 haplotype with the 1221 haplotype also appeared to increase risk for both IFG/IGT and type 2 diabetes. Contrary to what might be expected, quantitative trait analysis in the families found that transmission of the disease-related 1121 and 1112 haplotypes was associated with a reduced hip size and lower waist-to-hip ratio, respectively. This study supports the paradigm that specific haplotype combinations of calpain 10 variants increase risk of both IFG/IGT and type 2 diabetes. However, the relative infrequency of the "at-risk" combinations in the South Indian population suggests that calpain 10 is not a common determinant of susceptibility to type 2 diabetes.

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“…It has been shown that calpains are necessary for the cartilage mineralization mediated by chondrocytes. This mineralization process occurs through proteoglycan proteolysis achieved by calpain activity (Yasuda et al, 1995). Capn2 is involved in the major remodelling occurring during cartilage growth.…”

Section: Restricted Intense Expression At Later Developmental Stagesmentioning

confidence: 99%

Calpain 2 expression pattern and sub-cellular localization during mouse embryogenesis

Raynaud¹,

Marcilhac²,

Chébli³

et al. 2008

Int. J. Dev. Biol.

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Regulation of migration and proliferation by calpain has been shown in various cell types; however, no data are available concerning calpain 2 (CAPN2) localization in embryonic tissues. Here, we report the expression pattern of CAPN2 during mouse embryonic development. Expression of the capn2 gene is observed throughout embryonic development. From ES cells and the 8-cell stage to late neurulation stages, CAPN2 is expressed in the cytoplasm and nuclear compartments, with a clear co-localisation with chromatin. Whole-mount in situ hybridization analysis from E8.5 to 14.5 stages indicates high levels of capn2 expression in the nervous system, heart and mesodermal tissues. Up-regulation is maintained during later developmental stages in proliferating cells and in precursor cells involved in muscle (myoblasts) or bone formation (chondrocytes). At later developmental stages, elevated mRNA levels coincided with CAPN2 nuclear localization in these cell types, while differentiated cells maintained cytoplasmic expression. This detailed analysis reveals dynamic expression: nuclear localization was associated either with active cell mitosis in embryonic stem cells and early developmental stages or with precursor cells later during organogenesis. Thus, these data indicate that CAPN2 may represent a key factor in development from the first cell division.

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m-Calpain in Rat Growth Plate Chondrocyte Cultures: Its Involvement in the Matrix Mineralization Process

Cited by 24 publications

References 0 publications

Matrix Metalloproteinases Are Not Essential for Aggrecan Turnover during Normal Skeletal Growth and Development

Matrix Metalloproteinases Are Not Essential for Aggrecan Turnover during Normal Skeletal Growth and Development

Haplotype Combinations of Calpain 10 Gene Polymorphisms Associate With Increased Risk of Impaired Glucose Tolerance and Type 2 Diabetes in South Indians

Calpain 2 expression pattern and sub-cellular localization during mouse embryogenesis

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