Collagen XXVII Organises the Pericellular Matrix in the Growth Plate

Plumb, Darren A.; Ferrara, Laila; Torbica, Tanja; Knowles, Lynnette; Mironov, Aleksandr; Kadler, Karl E.; Briggs, Michael D.; Boot-Handford, Raymond P.

doi:10.1371/journal.pone.0029422

Cited by 45 publications

(46 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…19 In addition, deletion and mutation knock-in mice have been generated. 20 Mice heterozygous for a mutation that changed a conserved residue in the collagen domain were phenotypically normal, while the homozygous offspring displayed a slight disruption of the growth plate architecture. Moreover, mice that carried a heterozygous deletion of 87 amino acids were normal, but their homozygous counterparts displayed severe chondrodysplasia with midline defects and died shortly after birth due to respiratory problems.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, mice that carried a heterozygous deletion of 87 amino acids were normal, but their homozygous counterparts displayed severe chondrodysplasia with midline defects and died shortly after birth due to respiratory problems. 20 When the deletion allele was targeted in chondrocytes only, homozygous mice survived after birth but were significantly smaller, with short long bones, mild thoracic kyphosis, distortion of the pelvis and thoracic cage, and craniofacial defects such as a shorter snout and a domed skull. Similar to the point mutation mice, the homozygous cartilagespecific deletion mice had abnormal growth plate architecture, with severe flattening of the chondrocytes and disorganization of the collagen fibers in the pericellular matrix.…”

Section: Discussionmentioning

confidence: 99%

“…Similar to the point mutation mice, the homozygous cartilagespecific deletion mice had abnormal growth plate architecture, with severe flattening of the chondrocytes and disorganization of the collagen fibers in the pericellular matrix. 20 To date, there are no human disease phenotypes associated with mutations in COL27A1. However, based on its important role in chondrogenesis and cartilage to bone transition and its high conservation in vertebrates, several groups have hypothesized a role for COL27A1 in human disease and looked for potential disorders linked to mutations in COL27A1 in patients with various molecularly undefined chondrodysplasias.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Mutations in COL27A1 cause Steel syndrome and suggest a founder mutation effect in the Puerto Rican population

et al. 2014

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Mutations in COL27A1 cause Steel syndrome and suggest a founder mutation effect in the Puerto Rican population

et al. 2014

View full text Add to dashboard Cite

“…For in situ hybridization using radioactive 35 S-labeled RNA probes, the procedures described by Gagnon et al (32) were employed on humeri from P0.5 mice. The probes for in situ detection of Col10a1 mRNA (33) (originally generated in the laboratory of Kathryn Cheah, University of Hong Kong, Hong Kong), Runx2 mRNA (originally generated by the laboratory of Gerard Karsenty, Columbia University Medical Center, New York, NY), Mmp13 mRNA (2), and Col2a1 mRNA were obtained from D. Plumb (34).…”

Section: Histological Analysis (I)mentioning

confidence: 99%

ADAM17 Controls Endochondral Ossification by Regulating Terminal Differentiation of Chondrocytes

Hall

Hill

Otero

et al. 2013

Molecular and Cellular Biology

Self Cite

View full text Add to dashboard Cite

f Endochondral ossification is a highly regulated process that relies on properly orchestrated cell-cell interactions in the developing growth plate. This study is focused on understanding the role of a crucial regulator of cell-cell interactions, the membrane-anchored metalloproteinase ADAM17, in endochondral ossification. ADAM17 releases growth factors, cytokines, and other membrane proteins from cells and is essential for epidermal growth factor receptor (EGFR) signaling and for processing tumor necrosis factor alpha. Here, we report that mice lacking ADAM17 in chondrocytes (A17⌬Ch) have a significantly expanded zone of hypertrophic chondrocytes in the growth plate and retarded growth of long bones. This abnormality is caused by an accumulation of the most terminally differentiated type of chondrocytes that produces a calcified matrix. Inactivation of ADAM17 in osteoclasts or endothelial cells does not affect the zone of hypertrophic chondrocytes, suggesting that the main role of ADAM17 in the growth plate is in chondrocytes. This notion is further supported by in vitro experiments showing enhanced hypertrophic differentiation of primary chondrocytes lacking Adam17. The enlarged zone of hypertrophic chondrocytes in A17⌬Ch mice resembles that described in mice with mutant EGFR signaling or lack of its ligand transforming growth factor ␣ (TGF␣), suggesting that ADAM17 regulates terminal differentiation of chondrocytes during endochondral ossification by activating the TGF␣/EGFR signaling axis. Skeletal development is crucial to ensure optimal mobility and breathing, as well as protection of vital organs, such as the brain, spinal cord, lung, and heart. The axial and appendicular skeletons are formed through the generation of a cartilage intermediate, a process known as endochondral ossification, whereas the skull and clavicles are formed through intramembranous ossification (1-3). In the limb bud, which can be used as a model, endochondral ossification is initiated when mesenchymal precursor cells condense and the most central chondrocytes begin to differentiate. Eventually, this gives rise to different zones of chondrocytes in the growth plate, beginning with the resting zone, followed by the proliferating zone and the hypertrophic zone, in which chondrocytes secrete a type X collagen-rich matrix (1, 2). Once the hypertrophic chondrocytes mature into a terminally differentiated state and the lowermost cell layer becomes surrounded by mineral, the hypertrophic chondrocytes undergo apoptosis. This area in the developing long bone is directly adjacent to the primary center of ossification and is remodeled into trabecular bone as the invading vasculature supports the influx of osteoblasts and osteoclasts. In this process, the calcified matrix laid down by the hypertrophic chondrocytes is thought to be degraded through proteolytic activities, including MMP13 and MMP9 (4), while the remaining matrix provides a scaffold for the formation of trabecular bone. A secondary center of ossification develops after birth in m...

show abstract

“…During early development, type VI collagen is abundant throughout the cartilage matrix and then gradually localizes around the cell until it is found exclusively in the PCM of adult cartilage (Alexopoulos et al, 2009; Morrison et al, 1996; Sherwin et al, 1999). This process also occurs throughout the growth plate as the limb develops and is thought to play an important role in organizing the growth plate's proliferative zone (Plumb et al, 2011). While the localization of PCM components during development is a well-known phenomenon, the mechanism by which these molecules are organized and assembled remains an important unanswered question.…”

Section: Introductionmentioning

confidence: 99%

The structure and function of the pericellular matrix of articular cartilage

2014

View full text Add to dashboard Cite

Chondrocytes in articular cartilage are surrounded by a narrow pericellular matrix (PCM) that is both biochemically and biomechanically distinct from the extracellular matrix (ECM) of the tissue. While the PCM was first observed nearly a century ago, its role is still under investigation. In support of early hypotheses regarding its function, increasing evidence indicates that the PCM serves as a transducer of biochemical and biomechanical signals to the chondrocyte. Work over the past two decades has established that the PCM in adult tissue is defined biochemically by several molecular components, including type VI collagen and perlecan. On the other hand, the biomechanical properties of this structure have only recently been measured. Techniques such as micropipette aspiration, in situ imaging, computational modeling, and atomic force microscopy have determined that the PCM exhibits distinct mechanical properties as compared to the ECM, and that these properties are influenced by specific PCM components as well as disease state. Importantly, the unique relationships among the mechanical properties of the chondrocyte, PCM, and ECM in different zones of cartilage suggest that this region significantly influences the stress-strain environment of the chondrocyte. In this review, we discuss recent advances in the measurement of PCM mechanical properties and structure that further increase our understanding of PCM function. Taken together, these studies suggest that the PCM plays a critical role in controlling the mechanical environment and mechanobiology of cells in cartilage and other cartilaginous tissues, such as the meniscus or intervertebral disc.

show abstract

Collagen XXVII Organises the Pericellular Matrix in the Growth Plate

Cited by 45 publications

References 23 publications

Mutations in COL27A1 cause Steel syndrome and suggest a founder mutation effect in the Puerto Rican population

Mutations in COL27A1 cause Steel syndrome and suggest a founder mutation effect in the Puerto Rican population

ADAM17 Controls Endochondral Ossification by Regulating Terminal Differentiation of Chondrocytes

The structure and function of the pericellular matrix of articular cartilage

Contact Info

Product

Resources

About