Importance of Phosphorylation for Osteopontin Regulation of Biomineralization

Gericke, Arne; Qin, Chunlin; Spevak, Lyudmila; Fujimoto, Yukiji Karen; Butler, William T.; Sørensen, Esben S.; Boskey, Adele L.

doi:10.1007/s00223-004-1288-1

Cited by 270 publications

(263 citation statements)

References 65 publications

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“…The OPN protein backbone amide I and II bands (Gericke et al 2005;Arrondo and Goni 1999) are clear for all CPN (see Figure S2), including micellar calcium phosphate (Gebhardt et al 2011). The hydrated CPN samples also show enhanced absorbance at ~1645 cm -1 , where C=O group absorption in random coil, polyproline-II, or loop structures is expected, as well as water bending vibrations.…”

Section: Fourier Transform Infrared Spectroscopymentioning

confidence: 95%

Structural studies of hydrated samples of amorphous calcium phosphate and phosphoprotein nanoclusters

et al. 2016

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There are abundant examples of nanoclusters and inorganic microcrystals in biology.Their study under physiologically relevant conditions remains challenging due to their instability, the requirements of sample preparation and other intrinsic limitations of the techniques used. Advantages of using neutron diffraction and contrast matching to characterize biomaterials are highlighted in this article. We have applied these methods and complementary techniques to search for long-range order within nanoclusters of calcium phosphate sequestered by bovine phosphopeptides, derived from osteopontin or casein. Hydrated and dried samples with different nanocluster radii were analyzed and compared to samples of known calcium phosphate phases. The absence of a distinct diffraction pattern from the nanoclusters is consistent with the presence of amorphous calcium phosphate structure.

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Section: Fourier Transform Infrared Spectroscopymentioning

confidence: 95%

Structural studies of hydrated samples of amorphous calcium phosphate and phosphoprotein nanoclusters

et al. 2016

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“…Osteopontin typically inhibits growth of calcium-containing crystals in models of bone mineralization and nephrolithiasis (Beshensky et al 2001;Steitz et al 2002). Similar effects have recently been demonstrated in a gel-based model of hydroxyapatite crystal formation (Gericke et al 2005). Fewer studies support a stimulatory role for osteopontin in mineralization (Wozniak et al 2000).…”

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confidence: 88%

“…Osteopontin, particularly at high concentrations, directly inhibits hydroxyapatite crystal growth by coating existing crystals with highly anionic protein (Goldberg et al 1995;Gericke et al 2005). Lower concentrations of osteopontin may affect mineralization through other mechanisms.…”

Section: The Effect Of Osteopontin On Pyrophosphate and Transglutaminmentioning

confidence: 99%

Osteopontin promotes pathologic mineralization in articular cartilage

et al. 2007

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Calcium pyrophosphate dihydrate (CPPD) crystals are commonly found in osteoarthritic joint tissues, where they predict severe disease. Unlike other types of calcium phosphate crystals, CPPD crystals form almost exclusively in the pericellular matrix of damaged articular cartilage, suggesting a key role for the extracellular matrix milieu in their development. Osteopontin is a matricellular protein found in increased quantities in the pericellular matrix of osteoarthritic cartilage. Osteopontin modulates the formation of calcium-containing crystals in many settings. We show here that osteopontin stimulates ATP-induced CPPD crystal formation by chondrocytes in vitro. This effect is augmented by osteopontin's incorporation into extracellular matrix by transglutaminase enzymes, is only modestly affected by its phosphorylation state, and is inhibited by integrin blockers. Surprisingly, osteopontin stimulates transglutaminase activity in cultured chondrocytes in a dose responsive manner. As elevated levels of transglutaminase activity promote extracellular matrix changes that permit CPPD crystal formation, this is one possible mechanism of action. We demonstrate the presence of osteopontin in the pericellular matrix of chondrocytes adjacent to CPPD deposits and near active transglutaminases. Thus, osteopontin may play an important role in facilitating CPPD crystal formation in articular cartilage. KeywordsOsteopontin; Calcium pyrophosphate dihydrate; Transglutaminase; Osteoarthritis Pathologic matrix mineralization is a common occurrence in joints affected by late stage osteoarthritis. Of synovial fluids sampled at the time of knee replacement, for example, 60% contain pathologic calcium-containing crystals (Derfus et al. 2002). Both calcium pyrophosphate dihydrate (CPPD) and hydroxyapatite-like basic calcium phosphate (BCP) crystals occur in osteoarthritic joints. Although the role that calcium-containing crystals play in osteoarthritis is not fully understood, there is ample evidence to suggest that these crystals are active participants in joint damage. In vitro, calcium-containing crystals induce the release of catabolic cytokines and proteases from synovial cells and chondrocytes (Cheung 2001). Clinically, their presence predicts increased severity of joint damage and more rapid progression of joint destruction (Ledingham et al. 1993;Nalbant et al. 2003).Corresponding Author: Ann K. Rosenthal, MD Rheumatology Section/ cc-111W Zablocki VA Medical Center 5000 W. National Ave. Milwaukee, WI 53295-1000 TEL: 414-384-2000ann.rosenthal@med.va.gov. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply ...

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“…The sites of OPN phosphorylation are heterogeneous, and it is not known whether certain specific sites are critical. That said, phosphorylation of OPN appears necessary for various physiological functions, including migration of cancer cells (Al-Shami et al, 2005), adhesion and bone resorption by osteoclasts (Razzouk et al, 2002), inhibition of smooth muscle cell calcification (Jono et al, 2000) and regulation of mineralization (Gericke et al, 2005). Whether the PTMs play a role in immune cell function is yet to be discovered.…”

Section: Post-translational Modifications (Ptm)mentioning

confidence: 99%