Osteopenia and decreased bone formation in osteonectin-deficient mice

Delany, Anne M.; Amling, Michael; Priemel, Matthias; Howe, Chin C.; Baron, Roland; Canalis, Ernesto

doi:10.1172/jci7039

Cited by 288 publications

(184 citation statements)

References 54 publications

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“…1 were isolated from mice of similar age and weight (7 months of age; SPARC null, 30 g; wild type, 29 g). The compensation in body weight in SPARC-null mice reflects in part in the substantial loss of bone that has been reported in these animals (7). Another potential target for compensatory weight loss in SPARC-null mice is muscle (A.D.B., T. Nagy, and E.H.S., unpublished experiments).…”

Section: Resultsmentioning

confidence: 85%

“…In SPARC-null dermis, maintenance of weight in the presence of fat accumulation was attributed to a loss of connective tissue, e.g., collagen I. Clearly the substantial osteopenia in these mice is also a contributing factor (7). Enhanced levels of serum leptin paralleled larger deposits of fat, both of which were augmented with age.…”

Section: Discussionmentioning

confidence: 98%

“…SPARC-null mice display early onset cataractogenesis and osteopenia as well as accelerated wound closure in response to dermal excisional wounding (5)(6)(7)(8). Perturbations in the structure and composition of the ECM in the absence of SPARC have been implicated in each of these phenotypic abnormalities.…”

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confidence: 99%

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SPARC-null mice exhibit increased adiposity without significant differences in overall body weight

Bradshaw

Graves

Motamed

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

197

149

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Secreted protein acidic and rich in cysteine͞osteonectin͞BM-40 (SPARC) is a matrix-associated protein that elicits changes in cell shape, inhibits cell-cycle progression, and influences the synthesis of extracellular matrix (ECM). The absence of SPARC in mice gives rise to aberrations in the structure and composition of the ECM that result in generation of cataracts, development of severe osteopenia, and accelerated closure of dermal wounds. In this report we show that SPARC-null mice have greater deposits of s.c. fat and larger epididymal fat pads in comparison with wild-type mice. Similar to earlier studies of SPARC-null dermis, we observed a reduction in collagen I in SPARC-null fat pads in comparison with wild-type. Although elevated levels of serum leptin were observed in SPARC-null mice, their overall body weights were not significantly different from those of wild-type counterparts. The diameters of adipocytes from SPARC-null versus wild-type epididymal fat pads were 252 ؎ 61 and 161 ؎ 33 m (means ؎ SD), respectively, and there was an increase in adipocyte number within SPARC-null fat pads in comparison with wild-type pads. Thus the absence of SPARC appears to result in an increase in the size of individual adipocytes as well as an increase in the number of adipocytes per fat pad. In fat pads isolated from wild-type mice, SPARC mRNA was associated with both the stromal͞vascular and adipocyte fractions. We propose that SPARC limits the accumulation of adipose tissue in mice in part through its demonstrated effects on the regulation of cell shape and production of ECM.

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Section: Resultsmentioning

confidence: 85%

Section: Discussionmentioning

confidence: 98%

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SPARC-null mice exhibit increased adiposity without significant differences in overall body weight

Bradshaw

Graves

Motamed

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

197

149

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“…It is highly expressed in adult bone tissues and during processes involving tissue remodeling such as tumorigenesis and wound repair. Mice that are homozygous-null for SPARC are able to develop a relatively normal phenotype but soon develop cataracts (3), have impaired bone formation (4), and show severe deficiencies in wound repair (5,6). In vitro experiments have shown the influence of SPARC on several cell processes.…”

mentioning

confidence: 99%

The Novel SPARC Family Member SMOC-2 Potentiates Angiogenic Growth Factor Activity

Rocnik

Liu

Sato

et al. 2006

Journal of Biological Chemistry

109

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SMOC-2 is a novel member of the SPARC family of matricellular proteins. The purpose of this study was to determine whether SMOC-2 can modulate angiogenic growth factor activity and angiogenesis. SMOC-2 was localized in the extracellular periphery of cultured human umbilical vein endothelial cells (HUVECs). Ectopically expressed SMOC-2 was also secreted into the tissue culture medium. In microarray profiling experiments, a recombinant SMOC-2 adenovirus induced the expression of transcripts required for cell cycle progression in HUVECs. Consistent with a growth-stimulatory role for SMOC-2, its overexpression stimulated DNA synthesis in a dosedependent manner. Overexpressed SMOC-2 also synergized with vascular endothelial growth factor or with basic fibroblast growth factor to stimulate DNA synthesis. Ectopically expressed SMOC-2 stimulated formation of network-like structures as determined by in vitro matrigel angiogenesis assays. Fetal calf serum enhanced the stimulatory effect of overexpressed SMOC-2 in this assay. Conversely, small interference RNA directed toward SMOC-2 inhibited network formation and proliferation. The angiogenic activity of SMOC-2 was also examined in experimental mice by subdermal implantation of Matrigel plugs containing SMOC-2 adenovirus. SMOC-2 adenovirus induced a 3-fold increase in the number of cells invading Matrigel plugs when compared with a control adenoviral vector. Basic fibroblast growth factor and SMOC-2 elicited a synergistic effect on cell invasion. Taken together, our results demonstrate that SMOC-2 is a novel angiogenic factor that potentiates angiogenic effects of growth factors.

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“…However, postnatally BM-40-deficient mice develop cataracts with an abnormal cell surface-basement membrane interface (13)(14)(15) and severe osteopenia (16). These mice also display defects in wound healing (17,18) and in tissue remodeling (19,20).…”

mentioning

confidence: 99%

Characterization of SMOC-1, a Novel Modular Calcium-binding Protein in Basement Membranes

Vannahme¹,

Smyth²,

Miosge³

et al. 2002

Journal of Biological Chemistry

106

113

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We have isolated the novel gene SMOC-1 that encodes a secreted modular protein containing an EF-hand calcium-binding domain homologous to that in BM-40. It further consists of two thyroglobulin-like domains, a follistatin-like domain and a novel domain. Recombinant expression in human cells showed that SMOC-1 is a glycoprotein with a calcium-dependent conformation. Results from Northern blots, reverse transcriptase-PCR, and immunoblots revealed a widespread expression in many tissues. Immunofluorescence studies with an antiserum directed against recombinant human SMOC-1 demonstrated a basement membrane localization of the protein and additionally its presence in other extracellular matrices. Immunogold electron microscopy confirmed the localization of SMOC-1 within basement membranes in kidney and skeletal muscle as well as its expression in the zona pellucida surrounding the oocyte.

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Osteopenia and decreased bone formation in osteonectin-deficient mice

Cited by 288 publications

References 54 publications

SPARC-null mice exhibit increased adiposity without significant differences in overall body weight

SPARC-null mice exhibit increased adiposity without significant differences in overall body weight

The Novel SPARC Family Member SMOC-2 Potentiates Angiogenic Growth Factor Activity

Characterization of SMOC-1, a Novel Modular Calcium-binding Protein in Basement Membranes

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