Regulation of mesenchymal stem cell and chondrocyte differentiation by MIA

Tscheudschilsuren, Gerelsul; Bosserhoff, Anja‐Katrin; Schlegel, Jacqueline; Vollmer, David; Anton, A; Alt, Volker; Schnettler, Reinhard; Brandt, Jörg; Proetzel, Gabriele

doi:10.1016/j.yexcr.2005.09.017

Cited by 35 publications

(48 citation statements)

References 45 publications

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“…Dmp1 regulates extracellular matrix mineralization, calcium-phosphate homeostasis, and also serves as transcriptional regulator of dentin sialo-phosphoprotein (29,30). Similarly, otoraplin/cartilagederived retinoic acid-sensitive protein (Otor/CD-RAP), a proteoglycan involved in chondrogenesis (31), is increased by Wnt11 cells at all time points examined. Interestingly, in control cells, BMP treatment results in repression of Otor expression (supplemental Table S1).…”

Section: Wnt11 Enhances Bmp2-induced Osteoblast Maturation Andmentioning

confidence: 97%

Wnt11 Promotes Osteoblast Maturation and Mineralization through R-spondin 2

Friedman

Oyserman

Hankenson

2009

Journal of Biological Chemistry

106

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Wnt11 signals through both canonical (␤-catenin) and noncanonical pathways and is up-regulated during osteoblast differentiation and fracture healing. In these studies, we evaluated the role of Wnt11 during osteoblastogenesis. Wnt11 overexpression in MC3T3E1 pre-osteoblasts increases ␤-catenin accumulation and promotes bone morphogenetic protein (BMP)-induced expression of alkaline phosphatase and mineralization. Wnt11 dramatically increases expression of the osteoblast-associated genes Dmp1 (dentin matrix protein 1), Phex (phosphateregulating endopeptidase homolog), and Bsp (bone sialoprotein). Wnt11 also increases expression of Rspo2 (R-spondin 2), a secreted factor known to enhance Wnt signaling. Overexpression of Rspo2 is sufficient for increasing Dmp1, Phex, and Bsp expression and promotes bone morphogenetic protein-induced mineralization. Knockdown of Rspo2 abrogates Wnt11-mediated osteoblast maturation. Antagonism of T-cell factor (Tcf)/ ␤-catenin signaling with dominant negative Tcf blocks Wnt11-mediated expression of Dmp1, Phex, and Rspo2 and decreases mineralization. However, dominant negative Tcf fails to block the osteogenic effects of Rspo2 overexpression. These studies show that Wnt11 signals through ␤-catenin, activating Rspo2 expression, which is then required for Wnt11-mediated osteoblast maturation.Wnt signaling is a key regulator of osteoblast differentiation and maturation. In mesenchymal stem cell lines, canonical Wnt signaling by Wnt10b enhances osteoblast differentiation (1). Canonical Wnt signaling through ␤-catenin has also been shown to enhance the chondroinductive and osteoinductive properties of BMP2 2 (2, 3). During BMP2-induced osteoblast differentiation of mesenchymal stem cell lines, cross-talk between BMP and Wnt pathways converges through the interaction of Smad4 with ␤-catenin (2).Canonical Wnt signaling is also critical for skeletal development and homeostasis. During limb development, expression of Wnt3a in the apical ectodermal ridge of limb buds maintains cells in a highly proliferative and undifferentiated state (4, 5). Disruption of canonical Wnt signaling in Lrp5/Lrp6 compound knock-out mice results in limb-and digit-patterning defects (6). Wnt signaling is also involved in the maintenance of postnatal bone mass. Gain of function in the Wnt co-receptor Lrp5 leads to increased bone mass, whereas loss of Lrp5 function is associated with decreased bone mass and osteoporosis pseudoglioma syndrome (7,8). Mice with increased Wnt10b expression have increased trabecular bone, whereas Wnt10b-deficient mice have reduced trabecular bone (9). Similarly, mice nullizygous for the Wnt antagonist sFrp1 have increased trabecular bone accrual throughout adulthood (10).Although canonical Wnt signaling regulates osteoblastogenesis and bone formation, the profile of endogenous Wnts that play a role in osteoblast differentiation and maturation is not well described. During development, Wnt11 is expressed in the perichondrium and in the axial skeleton and sternum (11). Wnt11 expression is incr...

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Section: Wnt11 Enhances Bmp2-induced Osteoblast Maturation Andmentioning

confidence: 97%

Wnt11 Promotes Osteoblast Maturation and Mineralization through R-spondin 2

Friedman

Oyserman

Hankenson

2009

Journal of Biological Chemistry

106

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“…1 Being avascular with a very slow turnover at cellular and molecular levels, articular cartilage has limited capacity for self-repair. Many treatments have been applied to restore normal function to injured cartilage, including abrasion, drilling, and microfracture.…”

Section: Introductionmentioning

confidence: 99%

A novel injectable scaffold for cartilage tissue engineering using adipose‐derived adult stem cells

Wei

et al. 2007

Journal Orthopaedic Research

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Articular cartilage has a limited self-regenerative capacity. Thus, treatment of cartilage lesions is a major challenge. Tissue engineering using a variety of biomaterials is a promising solution to the problem of cartilage damage. In this in vitro study, we investigated the effect of the presence of cartilage-tissue chondroitin-sulfate (CS) in a fibrin scaffold on the differentiation of adipose-derived adult stem cells (ADAS cells) into chondrocytes. Isolated rabbit ADAS cells were cultured in fibrin matrices with and without CS for up to 14 days. ADAS cells differentiated into chondrocytes in both matrices, but cell proliferation, glycoaminoglycans content, and type II collagen expression were significantly higher in the fibrin-CS matrices than those in the fibrin matrices alone. Histological examination and scanning electronic microscopy revealed the fibrin-CS matrices exceeded in inducing differentiation of ADAS cells into chondrocytes in terms of tissue morphological characteristics. We concluded that the fibrin-CS matrices mimicking native cartilage extracellular matrix could act as a three-dimensional scaffold for cartilage tissue engineering and have the potential for promoting ADAS cells differentiation into chondrocytes. ß

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“…Later studies revealed that MIA is also expressed under healthy conditions in cartilage (21), where it is presumed to play a role in chondrocyte differentiation and cartilage matrix organization (22,23). MIA is produced and secreted exclusively by chondrocytes, and its expression is regulated similarly to that of the 2 major cartilage matrix proteins, type II collagen and aggrecan (21,23). The notion of a relationship between MIA and RA was first raised by Müller-Ladner et al (24), from a study whose results suggested that high serum levels of MIA in RA patients correlated with a more aggressive form of the disease.…”

mentioning

confidence: 99%

Endogenous HLA–DR–restricted presentation of the cartilage antigens human cartilage gp‐39 and melanoma inhibitory activity in the inflamed rheumatoid joint

Lierop¹,

Hoed²,

Houbiers³

et al. 2007

Arthritis & Rheumatism

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Objective. The cartilage proteins melanoma inhibitory activity (MIA) and human cartilage gp-39 (HC gp-39) are candidate autoantigens in rheumatoid arthritis (RA). The present study was undertaken to investigate the endogenous HLA-DR4-restricted presentation of these self proteins, in order to seek in vivo evidence in support of their potential immunologic role. The mechanisms that cause and sustain rheumatoid arthritis (RA) remain poorly elucidated. The association of the disease with certain class II major histocompatibility complex (MHC) haplotypes, however, strongly suggests that specific antigens are presented by antigen-presenting cells (APCs) to CD4ϩ T lymphocytes (1,2). Previous studies indicate that cartilage could be the source of some of these antigens in RA (3-7). In the present study we investigated the local presence and presentation of 2 cartilage-derived proteins that have distinct properties: human cartilage gp-39 (HC gp-39) and a protein called melanoma inhibitory activity (MIA).

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Regulation of mesenchymal stem cell and chondrocyte differentiation by MIA

Cited by 35 publications

References 45 publications

Wnt11 Promotes Osteoblast Maturation and Mineralization through R-spondin 2

Wnt11 Promotes Osteoblast Maturation and Mineralization through R-spondin 2

A novel injectable scaffold for cartilage tissue engineering using adipose‐derived adult stem cells

Endogenous HLA–DR–restricted presentation of the cartilage antigens human cartilage gp‐39 and melanoma inhibitory activity in the inflamed rheumatoid joint

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