A new player in cartilage homeostasis: adiponectin induces nitric oxide synthase type II and pro-inflammatory cytokines in chondrocytes

SummaryObjectiveRecent studies revealed a close connection between adipose tissue, adipokines and articular degenerative inflammatory diseases such as rheumatoid arthritis (RA) and osteoarthritis (OA). The goal of this work was to investigate the activity of adiponectin in human and murine chondrocytes and to study its functional role in the modulation of nitric oxide synthase type II (NOS2). For completeness, interleukin (IL)-6, IL-1β, matrix metalloproteinase (MMP)-2, MMP-3, MMP-9, tissue inhibitor of metalloproteinase (TIMP)-1, prostaglandin E2 (PGE2), leukotriene B4 (LTB4), tumor necrosis factor alpha (TNF)-α and monocyte chemoattractant protein-1 (MCP-1) accumulation have been evaluated in adiponectin-stimulated chondrocytes cell culture supernatants.MethodsMurine ATDC5 cell line, C28/I2, C20A4, TC28a2 human immortalized chondrocytes, and human cultured chondrocytes were used. Nitrite accumulation was determined by Griess reaction. Adiponectin receptors (AdipoRs) expression was evaluated by immunofluorescence microscopy and confirmed by reverse transcriptase-polymerase chain reaction. NOS2 expression was evaluated by Western blot analysis whereas cytokines, prostanoids and metalloproteinases production was evaluated by specific enzyme-linked immunosorbent assays.ResultsHuman and murine chondrocytes express functional AdipoRs. Adiponectin induces NOS2. This effect is inhibited by aminoguanidine, dexamethasone and by a selective inhibitor of phosphatidylinositol 3-kinase. In addition, adiponectin is able to increase IL-6, MMP-3, MMP-9 and MCP-1 by murine cultured chondrocytes whereas it was unable to modulate TNF-α, IL-1β, MMP-2, TIMP-1, PGE2 and LTB4 release.ConclusionsThese results bind more closely the interactions between fat-derived adipokines and articular inflammatory diseases, and suggest that adiponectin is a novel key element in the maintenance of cartilage homeostasis which might be considered as a potential therapeutical target in joint degenerative diseases

A geometric bound on F-term inflation

We discuss a general bound on the possibility to realise inflation in any minimal supergravity with F-terms. The derivation crucially depends on the sGoldstini, the scalar field directions that are singled out by spontaneous supersymmetry breaking. The resulting bound involves both slow-roll parameters and the geometry of the K\"ahler manifold of the chiral scalars. We analyse the inflationary implications of this bound, and in particular discuss to what extent the requirements of single field and slow-roll can both be met in F-term inflation.Comment: 14 pages, improved analysis, references added, matches published versio

Exact Superpotentials, Theories with Flavor and Confining Vacua

In this paper we study some interesting properties of the effective superpotential of N=1 supersymmetric gauge theories with fundamental matter, with the help of the Dijkgraaf--Vafa proposal connecting supersymmetric gauge theories with matrix models. We find that the effective superpotential for theories with N_f fundamental flavors can be calculated in terms of quantities computed in the pure (N_f=0) gauge theory. Using this property we compute in a remarkably simple way the exact effective superpotential of N=1 supersymmetric theories with fundamental matter and gauge group SU(N_c), at the point in the moduli space where a maximal number of monopoles become massless (confining vacua). We extend the analysis to a generic point of the moduli space, and show how to compute the effective superpotential in this general case.Comment: 16 pages, no figure

Moduli stabilization with positive vacuum energy

We study the effect of anomalous U(1) gauge groups in string theory compactification with fluxes. We find that, in a gauge invariant formulation, consistent AdS vacua appear breaking spontaneously supergravity. Non vanishing D-terms from the anomalous symmetry act as an uplifting potential and could allow for de Sitter vacua. However, we show that in this case the gravitino is generically (but not always) much heavier than the electroweak scale. We show that alternative uplifting scheme based on corrections to the Kahler potential can be compatible with a gravitino mass in the TeV range.Comment: 20 pages, 1 figur

Moduli stabilization with Fayet-Iliopoulos uplift

In the recent years, phenomenological models of moduli stabilization were proposed, where the dynamics of the stabilization is essentially supersymmetric, whereas an O'Rafearthaigh supersymmetry breaking sector is responsible for the "uplift" of the cosmological constant to zero. We investigate the case where the uplift is provided by a Fayet-Iliopoulos sector. We find that in this case the modulus contribution to supersymmetry breaking is larger than in the previous models. A first consequence of this class of constructions is for gauginos, which are heavier compared to previous models. In some of our explicit examples, due to a non-standard gauge-mediation type negative contribution to scalars masses, the whole superpartner spectrum can be efficiently compressed at low-energy. This provides an original phenomenology testable at the LHC, in particular sleptons are generically heavier than the squarks.Comment: 29 pages, 2 figure

Metastable de Sitter vacua in N=2 to N=1 truncated supergravity

We study the possibility of achieving metastable de Sitter vacua in general N=2 to N=1 truncated supergravities without vector multiplets, and compare with the situations arising in N=2 theories with only hypermultiplets and N=1 theories with only chiral multiplets. In N=2 theories based on a quaternionic manifold and a graviphoton gauging, de Sitter vacua are necessarily unstable, as a result of the peculiar properties of the geometry. In N=1 theories based on a Kahler manifold and a superpotential, de Sitter vacua can instead be metastable provided the geometry satisfies some constraint and the superpotential can be freely adjusted. In N=2 to N=1 truncations, the crucial requirement is then that the tachyon of the mother theory be projected out from the daughter theory, so that the original unstable vacuum is projected to a metastable vacuum. We study the circumstances under which this may happen and derive general constraints for metastability on the geometry and the gauging. We then study in full detail the simplest case of quaternionic manifolds of dimension four with at least one isometry, for which there exists a general parametrization, and study two types of truncations defining Kahler submanifolds of dimension two. As an application, we finally discuss the case of the universal hypermultiplet of N=2 superstrings and its truncations to the dilaton chiral multiplet of N=1 superstrings. We argue that de Sitter vacua in such theories are necessarily unstable in weakly coupled situations, while they can in principle be metastable in strongly coupled regimes.Comment: 40 pages, no figure

Effects of heavy modes on vacuum stability in supersymmetric theories

We study the effects induced by heavy fields on the masses of light fields in supersymmetric theories, under the assumption that the heavy mass scale is much higher than the supersymmetry breaking scale. We show that the square-masses of light scalar fields can get two different types of significant corrections when a heavy multiplet is integrated out. The first is an indirect level-repulsion effect, which may arise from heavy chiral multiplets and is always negative. The second is a direct coupling contribution, which may arise from heavy vector multiplets and can have any sign. We then apply these results to the sGoldstino mass and study the implications for the vacuum metastability condition. We find that the correction from heavy chiral multiplets is always negative and tends to compromise vacuum metastability, whereas the contribution from heavy vector multiplets is always positive and tends on the contrary to reinforce it. These two effects are controlled respectively by Yukawa couplings and gauge charges, which mix one heavy and two light fields respectively in the superpotential and the Kahler potential. Finally we also comment on similar effects induced in soft scalar masses when the heavy multiplets couple both to the visible and the hidden sector.Comment: LaTex, 24 pages, no figures; v2 some comments and references adde

Metastable supergravity vacua with F and D supersymmetry breaking

We study the conditions under which a generic supergravity model involving chiral and vector multiplets can admit viable metastable vacua with spontaneously broken supersymmetry and realistic cosmological constant. To do so, we impose that on the vacuum the scalar potential and all its first derivatives vanish, and derive a necessary condition for the matrix of its second derivatives to be positive definite. We study then the constraints set by the combination of the flatness condition needed for the tuning of the cosmological constant and the stability condition that is necessary to avoid unstable modes. We find that the existence of such a viable vacuum implies a condition involving the curvature tensor for the scalar geometry and the charge and mass matrices for the vector fields. Moreover, for given curvature, charges and masses satisfying this constraint, the vector of F and D auxiliary fields defining the Goldstino direction is constrained to lie within a certain domain. The effect of vector multiplets relative to chiral multiplets is maximal when the masses of the vector fields are comparable to the gravitino mass. When the masses are instead much larger or much smaller than the gravitino mass, the effect becomes small and translates into a correction to the effective curvature. We finally apply our results to some simple classes of examples, to illustrate their relevance.Comment: 40 pages; v2 some clarifications added in the introduction; v3 some typos correcte

Warping and F-term uplifting

We analyse the effective supergravity model of a warped compactification with matter on D3 and D7-branes. We find that the main effect of the warp factor is to modify the F-terms while leaving the D-terms invariant. Hence warped models with moduli stabilisation and a small positive cosmological constant resulting from a large warping can only be achieved with an almost vanishing D-term and a F-term uplifting. By studying string-motivated examples with gaugino condensation on magnetised D7-branes, we find that even with a vanishing D-term, it is difficult to achieve a Minkowski minimum for reasonable parameter choices. When coupled to an ISS sector the AdS vacua is uplifted, resulting in a small gravitino mass for a warp factor of order 10^-5.Comment: 24 pages, v3: typos, minor clarifications adde

Improved matrix-model calculation of the N=2 prepotential

We present a matrix-model expression for the sum of instanton contributions to the prepotential of an N=2 supersymmetric U(N) gauge theory, with matter in various representations. This expression is derived by combining the renormalization-group approach to the gauge theory prepotential with matrix-model methods. This result can be evaluated order-by-order in matrix-model perturbation theory to obtain the instanton corrections to the prepotential. We also show, using this expression, that the one-instanton prepotential assumes a universal form.Comment: 20 pages, LaTeX, 2 figure