Altered endochondral ossification in collagen X mouse models leads to impaired immune responses

Sweeney, Elizabeth; Campbell, Michelle R.; Watkins, Katherine E.; Hunter, Christopher A.; Jacenko, Olena

doi:10.1002/dvdy.21594

Cited by 17 publications

(51 citation statements)

References 104 publications

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“…Further, similar conclusions about the necessity of EO-derived components, e.g. cells and matrix molecules, were obtained through analyses of several mouse models with skeleto-hematopoietic defects ( Table 1), including mice with disrupted collagen X function in the HME (Jacenko et al 1993;Gress and Jacenko 2000;Jacenko et al 2002;Sweeney et al 2008;Sweeney et al 2010). Discussed below are the data describing which cell type(s), associated matrix and soluble factors are necessary for blood cell development in the marrow, including: multipotent stromal cells (fibroblasts, pericytes, reticular cells, and adipocytes), osteoblasts, chondrocytes, endothelial cells, and cells of hematopoietic origin (hematopoietic stem/progenitor cells (HSPC), osteoclasts and macrophages).…”

Section: Cells Of the Nichesupporting

confidence: 59%

“…However, the contribution of various matrix components, in particular the heparan sulfate proteoglycans (HSPG), in establishing reservoirs of soluble factors for cell signaling and/or retention of HSPCs has been well established (as reviewed in (Rodgers et al 2008) also see (Gordon et al 1988;Roberts et al 1988;Siczkowski et al 1992;Verfaillie 1993;Allouche and Bikfalvi 1995;Bruno et al 1995;Klein et al 1995;Gupta et al 1996;Gupta et al 1998;Borghesi et al 1999;Siebertz et al 1999;Zweegman et al 2004;Rodgers et al 2008;. In support, our laboratory has shown altered localization of both hyaluronan and HSPGs within the hypertrophic cartilage zone of the growth plates in the collagen X mouse models that display altered hematopoiesis (Jacenko et al 2001), which directly links EO and the hypertrophic cartilage matrix to hematopoiesis (Jacenko et al 1993;Gress and Jacenko 2000;Jacenko et al 2001;Jacenko et al 2002;Sweeney et al 2008;Sweeney et al 2010). Briefly, collagen X is a short chain, network forming collagen that is the major secreted matrix protein of hypertrophic chondrocytes and is localized to the hypertrophic cartilage/chondro-osseous region (Campbell et al 2004), where it is proposed to form a hexagonal lattice-like network in the matrix (Jacenko et al 1991;Chan, D. and Jacenko 1998).…”

Section: Chondrocytesmentioning

confidence: 62%

“…1B boxed) (Jacenko et al 1993;Nilsson et al 1997;Gress and Jacenko 2000;Nilsson et al 2001;Jacenko et al 2002;Yoshimoto et al 2003;Arai, F. et al 2004;Balduino et al 2005;Sweeney et al 2008;Kohler et al 2009;Lo Celso et al 2009;Xie et al 2009;Sweeney et al 2010). This skeleto-hematopoietic link is strongly supported by several animal models where alterations in process of EO leads to hematopoietic defects (Table 1), including mouse models with altered: collagen X (Jacenko et al 1993;Gress and Jacenko 2000;Jacenko et al 2002;Sweeney et al 2008;Sweeney et al 2010), parathyroid hormone related protein (PTHrP) receptor in osteoblasts (Calvi et al 2001;Calvi et al 2003;Kuznetsov et al 2004;Wu et al 2008), osteoblast numbers (Visnjic et al 2001;Visnjic et al 2004;Zhu et al 2007), bone morphogenic protein (BMP) receptor type 1A in marrow cells (Zhang, J. et al 2003), osteoclast function (Blin-Wakkach et al 2004;Mansour et al 2011), retinoic acid receptor gamma (Purton et al 2006;, G s  in ostoblasts (Wu et al 2008), Dicer in ostoblasts (Raaijmakers et al 2010), glypican-3 (Viviano et al 2005, and perlecan (Rodgers et al 2008). Table 1 p r e s e n t s a l i s t o f m o u s e m o d e l s w i t h d e f e c t s i n hematopoiesis due to alterations in a component within the niche environment.…”

Section: Coordinate Skeletal and Hematopoietic Developmentmentioning

confidence: 99%

“…Further, these assays confirmed a connection between osteoblasts and B cell development. To assess the contribution of osteoblasts to hematopoiesis in vivo, several different mouse models have been generated that either increase osteoblasts (Calvi et al 2001;Calvi et al 2003;Zhang, J. et al 2003), decrease osteoblasts (Visnjic et al 2001;Visnjic et al 2004), disrupt EO-based trabecular bone formation (Jacenko et al 1993;Gress and Jacenko 2000;Jacenko et al 2001;Jacenko et al 2002;Sweeney et al 2008;Sweeney et al 2010), alter osteoblast signaling (Wu et al 2008), or modify osteoblast RNA processing (Table 1) (Raaijmakers et al 2010). These in vivo models have confirmed that osteoblasts can support hematopoiesis, are involved in B lymphopoiesis, make pro-hematopoietic cytokines, make cell-cell contact with HSPCs, and moreover, have implicated osterix expressing osteoprogenitors as mediators of hematopoiesis.…”

Section: Osteoblastsmentioning

confidence: 99%

“…1). Hypertrophic chondrocytes and their matrix components are also essential for trabecular bone formation, and are proposed to be part of the osteoblast/lymphopoietic niche (Jacenko et al 2002;Rodgers et al 2008;Sweeney et al 2008;Sweeney et al 2010). Interestingly, hypertrophic chondrocytes have been described to trans-differentiate into osteoblasts (Roach 1992;Galotto et al 1994;Roach et al 1995;Roach and Erenpreisa 1996), and express osteoblast-like markers, e.g.…”

Section: Osteoblastsmentioning

confidence: 99%

See 4 more Smart Citations

Skeletogenesis and the Hematopoietic Niche

Sweeney¹,

Jacenko²

2012

Advances in Hematopoietic Stem Cell Research

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Section: Cells Of the Nichesupporting

confidence: 59%

Section: Chondrocytesmentioning

confidence: 62%

Section: Coordinate Skeletal and Hematopoietic Developmentmentioning

confidence: 99%

Section: Osteoblastsmentioning

confidence: 99%

Section: Osteoblastsmentioning

confidence: 99%

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Skeletogenesis and the Hematopoietic Niche

Sweeney¹,

Jacenko²

2012

Advances in Hematopoietic Stem Cell Research

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Heparan sulfate proteoglycans: A GAGgle of skeletal‐hematopoietic regulators

Rodgers

Antonio

Jacenko

2008

Developmental Dynamics

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This review summarizes our current understanding of the presence and function of heparan sulfate proteoglycans (HSPGs) in skeletal development and hematopoiesis. Although proteoglycans (PGs) comprise a large and diverse group of cell surface and matrix molecules, we chose to focus on HSPGs owing to their many proposed functions in skeletogenesis and hematopoiesis. Specifically, we discuss how HSPGs play predominant roles in establishing and regulating niches during skeleto-hematopoietic development by participating in distinct developmental processes such as patterning, compartmentalization, growth, differentiation, and maintenance of tissues. Special emphasis is placed on our novel hypothesis that mechanistically links endochondral skeletogenesis to the establishment of the hematopoietic stem cell (HSC) niche in the marrow. HSPGs may contribute to these developmental processes through their unique abilities to establish and mediate morphogen, growth factor, and cytokine gradients; facilitate signaling; provide structural stability to tissues; and act as molecular filters and barriers. Developmental TRIBUTE TO DR. ELIZABETH D. HAYDr. Elizabeth Dexter Hay, "Betty" to her friends, would often introduce her seminars on extracellular matrix (ECM) and epithelial-mesenchymal cell transformations by showing pictures of her cats asleep intertwined with a blanket. She would use this analogy to highlight the intimate association that exists between a cell and its ECM during development. She was a pioneer who brought forth the notion that the ECM is not just a static "stuffing between cells," but has interactive and instructive roles in development.Betty's contribution to the ECM field began with her seminal discoveries in the emerging field of electron microscopy. She worked with Keith Porter, George Palade, Don Fawcett, Susumo Ito, Jean-Paul Revel, and others to unravel the intricate microanatomy of the cell and its ECM. Once, when working with Jean-Paul Revel to extend autoradiography to the ultrastructural level, Betty noticed that tritiated proline was incorporated into collagen in the ECM outside of the cartilage cells. Betty went on to demonstrate that epithelial cells, as well as other non-fibroblastic cells, do secrete collagen. Moreover, in her descriptions of the development and structure of the various matrices, Betty brought forth the hypothesis that the ECM interacts with cells, and that through these interactions, the cells are instructed to modify their behavior. This notion was showcased in the "Epithelial-Mesenchymal Transformation Model" she proposed to describe the dramatic morphological transformations of epithelial cells suspended in collagen gels.Among her numerous scientific accomplishments, Betty can be considered a founder of the field of cell biology. Moreover, through her personal attributes and interactions with col- leagues and her protegees, Betty has set the standard for many a scientist. This review is a tribute to Betty, a friend, colleague, and mentor, and highlights our developing premi...

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Depletion of annexin A5, annexin A6, and collagen X causes no gross changes in matrix vesicle–mediated mineralization, but lack of collagen X affects hematopoiesis and the Th1/Th2 response

Grskovic

Kutsch

Frie

et al. 2012

Journal of Bone and Mineral Research

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Numerous biochemical studies have pointed to an essential role of annexin A5 (AnxA5), annexin A6 (AnxA6), and collagen X in matrix vesicle-mediated biomineralization during endochondral ossification and in osteoarthritis. By binding to the extracellular matrix protein collagen X and matrix vesicles, annexins were proposed to anchor matrix vesicles in the extracellular space of hypertrophic chondrocytes to initiate the calcification of cartilage. However, mineralization appears to be normal in mice lacking AnxA5 and AnxA6, whereas collagen X-deficient mice show only subtle alterations in the growth plate organization. We hypothesized that the simultaneous lack of AnxA5, AnxA6, and collagen X in vivo induces more pronounced changes in the growth plate development and the initiation of mineralization. In this study, we generated and analyzed mice deficient for AnxA5, AnxA6, and collagen X. Surprisingly, mice were viable, fertile, and showed no obvious abnormalities. Assessment of growth plate development indicated that the hypertrophic zone was expanded in Col10a1 À/À and AnxA5 À/À AnxA6 À/À Col10a1 À/À newborns, whereas endochondral ossification and mineralization were not affected in 13-day-and 1-month-old mutants. In peripheral quantitative computed tomography, no changes in the degree of biomineralization were found in femora of 1-month-and 1-year-old mutants even though the diaphyseal circumference was reduced in Col10a1 À/À and AnxA5 cells and peripheral T-helper cellswere increased in Col10a1 À/À and AnxA5Col10a1 À/À mutants, and activated splenic T cells isolated from Col10a1 À/À mice secreted elevated levels of IL-4 and GM-CSF. Hence, collagen X is needed for hematopoiesis during endochondral ossification and for the immune response, but the interaction of annexin A5, annexin A6, and collagen X is not essential for physiological calcification of growth plate cartilage. Therefore, annexins and collagen X may rather fulfill functions in growth plate cartilage not directly linked to the mineralization process. ß

show abstract

Altered endochondral ossification in collagen X mouse models leads to impaired immune responses

Cited by 17 publications

References 104 publications

Skeletogenesis and the Hematopoietic Niche

Skeletogenesis and the Hematopoietic Niche

Heparan sulfate proteoglycans: A GAGgle of skeletal‐hematopoietic regulators

Depletion of annexin A5, annexin A6, and collagen X causes no gross changes in matrix vesicle–mediated mineralization, but lack of collagen X affects hematopoiesis and the Th1/Th2 response

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