BCP crystals increase prostacyclin production and upregulate the prostacyclin receptor in OA synovial fibroblasts: potential effects on mPGES1 and MMP-13.

  title={BCP crystals increase prostacyclin production and upregulate the prostacyclin receptor in OA synovial fibroblasts: potential effects on mPGES1 and MMP-13.},
  author={Eamonn S. Molloy and Maria P. Morgan and Barry J. McDonnell and John M. O'Byrne and Geraldine Mccarthy},
  journal={Osteoarthritis and cartilage},
  volume={15 4},

Mechanism of basic calcium phosphate crystal-stimulated cyclo-oxygenase-1 up-regulation in osteoarthritic synovial fibroblasts.

It is suggested that non-selective COX inhibition may be preferable to COX-2 selective inhibition in BCP crystal-associated OA and that BCP crystals can augment PG production in OASF through induction ofCOX-1 and COx-2.

Mechanism of basic calcium phosphate crystal-stimulated matrix metalloproteinase-13 expression by osteoarthritic synovial fibroblasts: inhibition by prostaglandin E2

BCP crystal induction of MMP-13 expression may involve the ERK1/2 and p38 MAPK pathways and activation of nuclear factor κB; this upregulation of M MP-13 may contribute to the accelerated cartilage breakdown in BCP crystal-associated osteoarthritis.

Annexin 5 overexpression increased articular chondrocyte apoptosis induced by basic calcium phosphate crystals

Overexpression of A5 and the presence of BCP crystals observed in advanced osteoarthritis contributed to chondrocyte apoptosis, and the results suggest a new pathophysiological mechanism for calcium-containing crystal arthropathies.

International Union of Basic and Clinical Pharmacology. CIX. Differences and Similarities between Human and Rodent Prostaglandin E2 Receptors (EP1–4) and Prostacyclin Receptor (IP): Specific Roles in Pathophysiologic Conditions

The recent advances in studies using pharmacological approaches, genetically modified animals, and genome-wide association studies regarding the roles of IP and EP1–4 receptors in the immune, cardiovascular, nervous, gastrointestinal, respiratory, genitourinary, and musculoskeletal systems are discussed.

The role of inhibition by phosphocitrate and its analogue in chondrocyte differentiation and subchondral bone advance in Hartley guinea pigs

Results indicated that articular chondrocytes in Hartley guinea pigs exhibited a hypertrophic phenotype and recapitulated a developmental molecular program similar to the endochondral pathway of ossification, suggesting that PC and PC analogues exerted their OA disease-modifying activity, in part, by inhibiting this molecular program.

Determination of calcium in synovial fluid samples as an aid to diagnosing osteoarthritis.

This article investigates the use of o-cresolphthalein complexone (OCP), a colorimetric reagent, to quantify calcium from crystals isolated from synovial fluid samples as a means of identifying the presence of BCP and, hence, improving the diagnosis of OA.

Synovial membrane receptors as therapeutic targets: A review of receptor localization, structure, and function

  • S. KleineS. Budsberg
  • Medicine, Biology
    Journal of orthopaedic research : official publication of the Orthopaedic Research Society
  • 2017
The goal of this review is to outline synovial membrane receptor localization and local therapeutic modulation of these receptors, in order to stimulate further research into pharmacological management of arthropathies at the local level.

Point: Hydroxyapatite crystal deposition is intimately involved in the pathogenesis and progression of human osteoarthritis

Enhanced effort is needed to establish calcium-containing crystals as a therapeutic target in OA, as current data suggest an intimate association in its pathogenesis and progression.

Salivary Antioxidants and Metalloproteinases in Juvenile Idiopathic Arthritis

Children with JIA exhibited a significantly higher salivary antioxidant activity and significantly lower MMP levels, suggesting anti-TNF treatment may modulate the degradation process during the course of arthritis by inhibition of the activity of MMP.



Basic calcium phosphate crystal-induced prostaglandin E2 production in human fibroblasts: role of cyclooxygenase 1, cyclooxygenase 2, and interleukin-1beta.

Findings indicate that BCP crystals may be an important amplifier of PGE(2) production through induction of the COX enzymes and the proinflammatory cytokine IL-1beta.

Prostanoid-induced expression of matrix metalloproteinase-1 messenger ribonucleic acid in rat osteosarcoma cells.

Prostanoid-induced expression of the MMP-1 gene in the rat osteoblastic osteosarcoma cell line UMR 106-01 is examined and data suggest that PGE2 stimulation of M MP-1 synthesis is due to activation of MMP -1 gene transcription and a subsequent marked increase in Mmp-1 mRNA abundance.

Prostacyclin Inhibits the Production of MMP-9 Induced by Phorbol Ester through Protein Kinase A Activation, but Does Not Affect the Production of MMP-2 in Human Cultured Mesangial Cells

Prostacyclin plays an important role in inflammatory glomerular disorders by regulating the metabolism of ECM in matrix metalloproteinase (MMP)-9 and MMP-2 in human cultured mesangial cells.

EP2/EP4 signalling inhibits monocyte chemoattractant protein-1 production induced by interleukin 1β in synovial fibroblasts

Activation of EP2/EP4 receptors down regulates the expression of MCP-1 in IL1β stimulated SF, while PGE2 pharmacological inhibition cuts off this signalling pathway and results in a superinduction of M CP-1 expression.

Induction of Matrix Metalloproteinase-8 in Human Fibroblasts by Basic Calcium Phosphate and Calcium Pyrophosphate Dihydrate Crystals: Effect of Phosphocitrate

The expression of MMP-8 in HF and its dose-dependent upregulation by basic calcium phosphate (BCP) and calcium pyrophosphate dihydrate (CPPD) crystals which arc markers of severe joint degeneration in ostcoarthritis are shown.

Cyclooxygenase 2-dependent prostaglandin E2 modulates cartilage proteoglycan degradation in human osteoarthritis explants.

The data suggest that induction of synovial COX-2-produced PGE(2) is one mechanism by which IL-1 beta modulates cartilage proteoglycan degradation in OA.

Basic calcium phosphate crystals activate human osteoarthritic synovial fibroblasts and induce matrix metalloproteinase-13 (collagenase-3) in adult porcine articular chondrocytes

These data confirm the ability of BCP crystals to activate HOAS, leading to the induction of mitogenesis and MMP-1 production and suggest that B CP crystals act synergistically with IL1α and TNFα to promote MMP production and subsequent joint degeneration.

Basic calcium phosphate crystals up-regulate metalloproteinases but down-regulate tissue inhibitor of metalloproteinase-1 and -2 in human fibroblasts.

The ability of BCP to induce the synthesis of degradative MMPs while down-regulating the synthesisof the naturally occurring counterpart TIMPs may explain the changes consistent with a role of B CP crystal in the pathogenesis of degenerative changes in osteoarthritis.

Microsomal Prostaglandin E Synthase-1 Is a Major Terminal Synthase That Is Selectively Up-Regulated During Cyclooxygenase-2-Dependent Prostaglandin E2 Production in the Rat Adjuvant-Induced Arthritis Model

Results show that mPGES-1 is up-regulated throughout the development of AIA and suggest that it plays a major role in the elevated production of PGE2 in this model.

Altered pain perception and inflammatory response in mice lacking prostacyclin receptor

It is established that prostacyclin is an antithrombotic agent in vivo and evidence for its role as a mediator of inflammation and pain is provided.