Complement Cls, a classical enzyme with novel functions at the endochondral ossification center: immunohistochemical staining of activated Cls with a neoantigen-specific antibody

Sakiyama, Hisako; Nakagawa, Kōichi; Kuriiwa, Kazuko; Imai, Kazushi; Okada, Yasunori; Tsuchida, Toyomitsu; Moriya, Hideshige; Imajoh‐Ohmi, Shinobu

doi:10.1007/s004410050841

Cited by 23 publications

(30 citation statements)

References 20 publications

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“…Chondrocytederived matrix metalloproteinases initiate this chondrolysis process (Hembry et al 1986;Blair et al 1989;Cameron et al 1989). We have also shown that C1s has the ability to degrade extracellular components of cartilage matrix (Yamaguchi et al 1990;Sakiyama et al 1997). Increased production of C1s by hypertrophic chondrocytes is pertinent to the proposed function of C1s.…”

Section: Discussionmentioning

confidence: 96%

Coordinated change between complement C1s production and chondrocyte differentiation in vitro

Nakagawa¹,

Sakiyama²,

Fukazawa³

et al. 1997

Cell and Tissue Research

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In vitro synthesis of the first component of complement C1s was examined by using hamster epiphyseal chondrocytes (HAC) and human chondrosarcoma cell line HCS-2/8. Hamster and human C1s produced by the cells were quantified by immunoblotting and sandwich enzyme-linked immunosorbent assay (ELISA), respectively. It was possible to measure active and inactive C1s by sandwich ELISA, when we used anti-human C1s monoclonal antibodies, M241 recognizing only active C1s, and M365 and M81 recognizing both active and inactive C1s. Approximately 40% of C1s secreted from HCS-2/8 was found to be activated in the culture medium, whereas C1s from HAC was not. C1s production increased in accordance with chondrocyte differentiation induced by ascorbic acid. In contrast, transforming growth factor-beta1 and basic fibroblast growth factor, which inhibited differentiation, suppressed C1s production. These results confirmed our previous observation showing that C1s synthesis increased with differentiation into hypertrophic chondrocytes in vivo.

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Section: Discussionmentioning

confidence: 96%

Coordinated change between complement C1s production and chondrocyte differentiation in vitro

Nakagawa¹,

Sakiyama²,

Fukazawa³

et al. 1997

Cell and Tissue Research

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“…Immunohistochemical studies clearly indicated that complement was activated during enchondral ossification, possibly for the modulation of apoptosis (74,75). These studies indicated that some interaction of the complement system with bone cells exists.…”

Section: Complement and Bone Biologymentioning

confidence: 95%

New Insights of an Old Defense System: Structure, Function, and Clinical Relevance of the Complement System

Ehrnthaller

Ignatius

Gebhard

et al. 2010

Mol Med

188

154

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The complement system was discovered a century ago as a potent defense cascade of innate immunity. After its first description, continuous experimental and clinical research was performed, and three canonical pathways of activation were established. Upon activation by traumatic or surgical tissue damage, complement reveals beneficial functions of pathogen and danger defense by sensing and clearing injured cells. However, the latest research efforts have provided a more distinct insight into the complement system and its clinical subsequences. Complement has been shown to play a significant role in the pathogenesis of various inflammatory processes such as sepsis, multiorgan dysfunction, ischemia/reperfusion, cardiovascular diseases and many others. The three well-known activation pathways of the complement system have been challenged by newer findings that demonstrate direct production of central complement effectors (for example, C5a) by serine proteases of the coagulation cascade. In particular, thrombin is capable of producing C5a, which not only plays a decisive role on pathogens and infected/damaged tissues, but also acts systemically. In the case of uncontrolled complement activation, "friendly fire" is generated, resulting in the destruction of healthy host tissue. Therefore, the traditional research that focuses on a mainly positive-acting cascade has now shifted to the negative effects and how tissue damage originated by the activation of the complement can be contained. In a translational approach including structure-function relations of this ancient defense system, this review provides new insights of complement-mediated clinical relevant diseases and the development of complement modulation strategies and current research aspects.

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“…Although osteoimmunology is gaining interest, not much is known about the role of the complement system in the growth plate 40. The complement system, and more specifically C1, seems to contribute to the turnover of cartilage into bone during endochondral ossification because several studies have shown that C1 is present in epiphyseal cartilage41 and ossification centers 42. How these systems affect chondrocyte proliferation and hypertrophy and facilitate differences in longitudinal growth and final height remains to be determined.…”

Section: Discussionmentioning

confidence: 99%

Growth plate expression profiling: Large and small breed dogs provide new insights in endochondral bone formation

Teunissen

Riemers

Leenen

et al. 2017

Journal Orthopaedic Research

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The difference in the adult height of mammals, and hence in endochondral bone formation, is not yet fully understood and may serve to identify targets for bone and cartilage regeneration. In line with this hypothesis, the intra‐species disparity between the adult height of Great Danes and Miniature Poodles was investigated at a transcriptional level. Microarray analysis of the growth plate of five Great Danes and five Miniature Poodles revealed 2,981 unique genes that were differentially expressed, including many genes with an unknown role in skeletal development. A signaling pathway impact analysis indicated activation of the cell cycle, extracellular matrix receptor interaction and the tight junction pathway, and inhibition of pathways associated with inflammation and the complement cascade. In additional validation steps, the gene expression profile of the separate growth plate zones for both dog breeds were determined. Given that the BMP signaling is known for its crucial role in skeletal development and fracture healing, and BMP‐2 is used in orthopaedic and spine procedures for bone augmentation, further investigations concentrated on the BMP pathway.The canonical BMP‐2 and BMP‐6 signaling pathway was activated in the Great Danes compared to Miniature Poodles. In conclusion, investigating the differential expression of genes involved in endochondral bone formation in small and large breed dogs, could be a game changing strategy to provide new insights in growth plate development and identify new targets for bone and cartilage regeneration. © 2017 The Authors. Journal of Orthopaedic Research® published by Wiley Periodicals, Inc. on behalf of the Orthopaedic Research Society. J Orthop Res 36:138–148, 2018.

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Complement Cls, a classical enzyme with novel functions at the endochondral ossification center: immunohistochemical staining of activated Cls with a neoantigen-specific antibody

Cited by 23 publications

References 20 publications

Coordinated change between complement C1s production and chondrocyte differentiation in vitro

Coordinated change between complement C1s production and chondrocyte differentiation in vitro

New Insights of an Old Defense System: Structure, Function, and Clinical Relevance of the Complement System

Growth plate expression profiling: Large and small breed dogs provide new insights in endochondral bone formation

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