Untitled

Brochhausen, Christoph; Neuland, Pia; Kirkpatrick, Charles James; Nüsing, Rolf M.; Klaus, Günter

doi:10.1186/ar1948

Cited by 47 publications

(12 citation statements)

References 50 publications

(46 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Expression of these enzymes in growth plate and in normal or pathological articular chondrocytes has been detected previously [26], [56]–[59]. In rat tibia growth plates, COX-1 was strongly expressed in the reserve zone, while only moderate COX-2 expression was detected in the reserve zone [57]. In cultured rat growth plate chondrocytes, cell proliferation was inhibited by treatment with SC-236, a COX-2 selective inhibitor, but not with SC-560, a COX-1 selective inhibitor [57].…”

Section: Discussionmentioning

confidence: 91%

“…In cultured rat growth plate chondrocytes, cell proliferation was inhibited by treatment with SC-236, a COX-2 selective inhibitor, but not with SC-560, a COX-1 selective inhibitor [57]. Proliferation of the cultured rat growth plate chondrocytes could be stimulated with PGE 2 or with a selective EP1 agonists [57]. Consistent with a COX-2 proliferative effect on growth plate chondrocytes, treatment of chicken growth plate chondrocytes with PGE 2 inhibited Type X collagen, VEGF, and MMP-13 expression indicating that PGE 2 treatment was inhibiting chondrocyte differentiation [60].…”

Section: Discussionmentioning

confidence: 93%

“…In rat tibia growth plates, COX-1 was strongly expressed in the reserve zone, while only moderate COX-2 expression was detected in the reserve zone [57]. In cultured rat growth plate chondrocytes, cell proliferation was inhibited by treatment with SC-236, a COX-2 selective inhibitor, but not with SC-560, a COX-1 selective inhibitor [57]. Proliferation of the cultured rat growth plate chondrocytes could be stimulated with PGE 2 or with a selective EP1 agonists [57].…”

Section: Discussionmentioning

confidence: 93%

See 2 more Smart Citations

Immunohistochemical Localization of Key Arachidonic Acid Metabolism Enzymes during Fracture Healing in Mice

Hao

O’Connor

2014

PLoS ONE

View full text Add to dashboard Cite

This study investigated the localization of critical enzymes involved in arachidonic acid metabolism during the initial and regenerative phases of mouse femur fracture healing. Previous studies found that loss of cyclooxygenase-2 activity impairs fracture healing while loss of 5-lipoxygenase activity accelerates healing. These diametric results show that arachidonic acid metabolism has an essential function during fracture healing. To better understand the function of arachidonic acid metabolism during fracture healing, expression of cyclooxygenase-1 (COX-1), cyclooxygenase -2 (COX-2), 5-lipoxygenase (5-LO), and leukotriene A4 hydrolase (LTA4H) was localized by immunohistochemistry in time-staged fracture callus specimens. All four enzymes were detected in leukocytes present in the bone marrow and attending inflammatory response that accompanied the fracture. In the tissues surrounding the fracture site, the proportion of leukocytes expressing COX-1, COX-2, or LTA4H decreased while those expressing 5-LO remained high at 4 and 7 days after fracture. This may indicate an inflammation resolution function for 5-LO during fracture healing. Only COX-1 was consistently detected in fracture callus osteoblasts during the later stages of healing (day 14 after fracture). In contrast, callus chondrocytes expressed all four enzymes, though 5-LO appeared to be preferentially expressed in newly differentiated chondrocytes. Most interestingly, osteoclasts consistently and strongly expressed COX-2. In addition to bone surfaces and the growth plate, COX-2 expressing osteoclasts were localized at the chondro-osseous junction of the fracture callus. These observations suggest that arachidonic acid mediated signaling from callus chondrocytes or from callus osteoclasts at the chondro-osseous junction regulate fracture healing.

show abstract

Section: Discussionmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 93%

See 1 more Smart Citation

Immunohistochemical Localization of Key Arachidonic Acid Metabolism Enzymes during Fracture Healing in Mice

Hao

O’Connor

2014

PLoS ONE

View full text Add to dashboard Cite

show abstract

“…Studies investigating the roles of cyclooxygenases and the effects of prostaglandins on ( in vitro ) chondrogenic differentiation have mainly focussed on COX-2 (inhibition) and PGE 2 [ 14 – 20 ]. However, the contribution of COX-1 and other prostaglandins in chondrogenic differentiation is largely ignored.…”

Section: Introductionmentioning

confidence: 99%

The Role of Prostaglandins and COX-Enzymes in Chondrogenic Differentiation of ATDC5 Progenitor Cells

et al. 2016

View full text Add to dashboard Cite

ObjectivesNSAIDs are used to relieve pain and decrease inflammation by inhibition of cyclooxygenase (COX)-catalyzed prostaglandin (PG) synthesis. PGs are fatty acid mediators involved in cartilage homeostasis, however the action of their synthesizing COX-enzymes in cartilage differentiation is not well understood. In this study we hypothesized that COX-1 and COX-2 have differential roles in chondrogenic differentiation.MethodsATDC5 cells were differentiated in the presence of COX-1 (SC-560, Mofezolac) or COX-2 (NS398, Celecoxib) specific inhibitors. Specificity of the NSAIDs and inhibition of specific prostaglandin levels were determined by EIA. Prostaglandins were added during the differentiation process. Chondrogenic outcome was determined by gene- and protein expression analyses.ResultsInhibition of COX-1 prevented Col2a1 and Col10a1 expression. Inhibition of COX-2 resulted in decreased Col10a1 expression, while Col2a1 remained unaffected. To explain this difference expression patterns of both COX-enzymes as well as specific prostaglandin concentrations were determined. Both COX-enzymes are upregulated during late chondrogenic differentiation, whereas only COX-2 is briefly expressed also early in differentiation. PGD2 and PGE2 followed the COX-2 expression pattern, whereas PGF2α and TXA2 levels remained low. Furthermore, COX inhibition resulted in decreased levels of all tested PGs, except for PGD2 and PGF2α in the COX-1 inhibited condition. Addition of PGE2 and PGF2α resulted in increased expression of chondrogenic markers, whereas TXA2 increased expression of hypertrophic markers.ConclusionsOur findings point towards a differential role for COX-enzymes and PG-production in chondrogenic differentiation of ATDC5 cells. Ongoing research is focusing on further elucidating the functional partition of cyclooxygenases and specific prostaglandin production.

show abstract

“…It has been shown that PGE 2 receptors (EP1-4) are expressed in both growth plates and primary chondrocytes [39]. Stimulation of human articular chondrocytes with PGE 2 through the EP2 receptor suppressed proteoglycan accumulation and synthesis [40].…”

Section: Discussionmentioning

confidence: 99%

Prostaglandin F2 receptor (FP) signaling regulates Bmp signaling and promotes chondrocyte differentiation

Kim

Shim

2015

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

View full text Add to dashboard Cite

Prostaglandins are a group of lipid signaling molecules involved in various physiological processes. In addition, prostaglandins have been implicated in the development and progression of diseases including cancer, cardiovascular disease, and arthritis. Prostaglandins exert their effects through the activation of specific G protein-coupled receptors (GPCRs). In this report, we examined the role of prostaglandin F2α receptor (FP) signaling as a regulator of chondrocyte differentiation. We found that FP expression was dramatically induced during the differentiation of chondrocytes and was up-regulated in cartilages. Forced expression of FP in ATDC5 chondrogenic cell line resulted in the increased expression of differentiation-related genes and increased synthesis of the extracellular matrix (ECM) regardless of the presence of insulin. Similarly, PGF2α treatment induced the expression of chondrogenic marker genes. In contrast, knockdown of endogenous FP expression suppressed the expression of chondrocyte marker genes and ECM synthesis. Organ culture of cartilage rudiments revealed that PGF2α induces chondrocyte hypertrophy. Additionally, FP overexpression increased the levels of Bmp-6, phospho-Smad1/5, and Bmpr1a, while knockdown of FP reduced expression of those genes. These results demonstrate that up-regulation of FP expression plays an important role in chondrocyte differentiation and modulates Bmp signaling.

show abstract

Untitled

Cited by 47 publications

References 50 publications

Immunohistochemical Localization of Key Arachidonic Acid Metabolism Enzymes during Fracture Healing in Mice

Immunohistochemical Localization of Key Arachidonic Acid Metabolism Enzymes during Fracture Healing in Mice

The Role of Prostaglandins and COX-Enzymes in Chondrogenic Differentiation of ATDC5 Progenitor Cells

Prostaglandin F2 receptor (FP) signaling regulates Bmp signaling and promotes chondrocyte differentiation

Contact Info

Product

Resources

About