Mechanically Strained Cells of the Osteoblast Lineage Organize Their Extracellular Matrix Through Unique Sites of αVβ3-Integrin Expression

Woźniak, Magdalena; Fausto, Aurora; Carron, Christopher P.; Meyer, Deborah M.; Hruska, Keith A.

doi:10.1359/jbmr.2000.15.9.1731

Cited by 120 publications

(102 citation statements)

References 77 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…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). It is likely that high levels of soluble osteopontin act directly on crystal nucleation or growth.…”

Section: Nih Public Accessmentioning

confidence: 55%

“…They showed this early pericellular mineralization process was dependent on the αvβ3 integrin (Wozniak et al 2000). To determine if the effects of osteopontin in our system were integrin-dependent, we blocked integrin binding with an antagonist peptide.…”

Section: The Role Of αVβ3 Integrin In Osteopontin's Effectsmentioning

confidence: 99%

“…and is known to act as a signaling protein and cytokine, as well as a regulator of mineralization (Denhardt et al 2001). Osteopontin interacts with the αvβ3 integrin (Wozniak et al 2000) and mediates cell adhesion and differentiation, which in turn could alter cell phenotype and matrix mineralization. In osteoblasts, osteopontin production is coordinately regulated with elaboration of inorganic pyrophosphate, a potent inhibitor of hydroxyapatite crystal formation Harmey et al 2004).…”

mentioning

confidence: 99%

See 2 more Smart Citations

Osteopontin promotes pathologic mineralization in articular cartilage

et al. 2007

View full text Add to dashboard Cite

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 ...

show abstract

Section: Nih Public Accessmentioning

confidence: 55%

Section: The Role Of αVβ3 Integrin In Osteopontin's Effectsmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Osteopontin promotes pathologic mineralization in articular cartilage

et al. 2007

View full text Add to dashboard Cite

show abstract

“…FAK is known be critical to integrin clustering as well being a potent signaling molecule with important kinase activity and several sites of tyrosine phosphorylation (Schaller, 1996;Schlaepfer et al, 1999). FAK is known to be involved in cell growth, survival and migration and is increasingly suspected to be involved in mechanotransduction in a number of cells (Lee et al, 2000;Gerthoffer and Gunst, 2001;Keller et al, 2001;Orr and Murphy-Ullrich, 2004) including bone cells (Wozniak et al, 2000;Rezzonico et al, 2003). When activated, FAK autophosphorylates tyrosine 397 which allows interaction with a number of src-family proteins and other molecules with SH2 domains (src homology 2, a specific sequence involved in binding to a phosphorylated tyrosine).…”

Section: Integrins and Integrin Associated Proteinsmentioning

confidence: 99%

Molecular pathways mediating mechanical signaling in bone

Rubin

Jacobs

2006

Gene

400

303

View full text Add to dashboard Cite

Bone tissue has the capacity to adapt to its functional environment such that its morphology is "optimized" for the mechanical demand. The adaptive nature of the skeleton poses an interesting set of biological questions (e.g., how does bone sense mechanical signals, what cells are the sensing system, what are the mechanical signals that drive the system, what receptors are responsible for transducing the mechanical signal, what are the molecular responses to the mechanical stimuli). Studies of the characteristics of the mechanical environment at the cellular level, the forces that bone cells recognize, and the integrated cellular responses are providing new information at an accelerating speed. This review first considers the mechanical factors that are generated by loading in the skeleton, including strain, stress and pressure. Mechanosensitive cells placed to recognize these forces in the skeleton, osteoblasts, osteoclasts, osteocytes and cells of the vasculature are reviewed. The identity of the mechanoreceptor(s) is approached, with consideration of ion channels, integrins, connexins, the lipid membrane including caveolar and noncaveolar lipid rafts and the possibility that altering cell shape at the membrane or cytoskeleton alters integral signaling protein associations. The distal intracellular signaling systems on-line after the mechanoreceptor is activated are reviewed, including those emanating from G-proteins (e.g., intracellular calcium shifts), MAPKs, and nitric oxide. The ability to harness mechanical signals to improve bone health through devices and exercise is broached. Increased appreciation of the importance of the mechanical environment in regulating and determining the structural efficacy of the skeleton makes this an exciting time for further exploration of this area.

show abstract

“…31,82,105 The link between mechanical stimulation and biochemical response has recently focused more acutely on the cytoskeleton 2,6,34,44,88,121 and its associated extracellular matrix-cell connections. 24,85,116,118 Of particular interest is the manner in which forces are transmitted into cells from the extracellular environment. One of these links is through the focal adhesion complexes, which are a heterocomplex of proteins including paxillin, vinculin, talin, and the transmembrane integrins.…”

Section: Mechanotransductionmentioning

confidence: 99%

Nanoscale Intracellular Organization and Functional Architecture Mediating Cellular Behavior

LeDuc

Bellin

2006

Ann Biomed Eng

View full text Add to dashboard Cite

Abstract-Cells function based on a complex set of interactions that control pathways resulting in ultimate cell fates including proliferation, differentiation, and apoptosis. The interworkings of this immensely dense network of intracellular molecules are influenced by more than random protein and nucleic acid distribution where their interactions culminate in distinct cellular function. By probing the design of these biological systems from an engineering perspective, researchers can gain great insight that will aid in building and utilizing systems that are on this size scale where traditional large-scale rules may fail to apply. The organized interaction and gradient distribution in intracellular space imply a structural architecture that modulates cellular processes by influencing biochemical interactions including transport and binding-reactions. One significant structure that plays a role in this modulation is the cell cytoskeleton. Here, we discuss the cytoskeleton as a central and integrating functional structure in influencing cell processes and we describe technology useful for probing this structure. We explain the nanometer scale science of cytoskeletal structure with respect to intracellular organization, mechanotransduction, cytoskeletal-associated proteins, and motor molecules, as well as nano-and microtechnologies that are applicable for experimental studies of the cytoskeleton. This biological architecture of the cytoskeleton influences molecular, cellular, and physiological processes through structured multimodular and hierarchical principles centered on these functional filaments. Through investigating these organic systems that have evolved over billions of years, understanding in biology, engineering, and nanometer-scaled science will be advanced.

show abstract

Mechanically Strained Cells of the Osteoblast Lineage Organize Their Extracellular Matrix Through Unique Sites of αVβ3-Integrin Expression

Abstract: ABSTRACT

Cited by 120 publications

References 77 publications

Osteopontin promotes pathologic mineralization in articular cartilage

Osteopontin promotes pathologic mineralization in articular cartilage

Molecular pathways mediating mechanical signaling in bone

Nanoscale Intracellular Organization and Functional Architecture Mediating Cellular Behavior

Contact Info

Product

Resources

About