Lysophosphatidic Acid Receptor Type 1 (LPA1) Plays a Functional Role in Osteoclast Differentiation and Bone Resorption Activity

David, Marion; Machuca-Gayet, Irma; Kikuta, Junichi; Ottewell, Penelope D.; Mima, Fuka; Leblanc, Raphaël; Bonnelye, Edith; Ribeiro, J. L.; Holen, Ingunn; López-Vales, Rubén; Jurdic, Pierre; Chun, Jerold; Clézardin, Philippe; Ishii, Masaru; Peyruchaud, Olivier

doi:10.1074/jbc.m113.533232

Cited by 39 publications

(43 citation statements)

References 77 publications

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“…The association between CD97 and LPAR‐1 was found to lead to enhanced LPA‐dependent activation of Rho and ERK. LPA receptors are the cognate receptors for LPA, and LPA modulates bone homeostasis by the activation of LPAR‐1 in osteoclasts . In that recent report, the investigators found that BM cells from LPAR‐1–KO mice formed fewer osteoclasts in vitro, and that this was specific to the type 1 receptor.…”

Section: Discussionmentioning

confidence: 97%

Contradictory Role of CD97 in Basal and Tumor Necrosis Factor–Induced Osteoclastogenesis In Vivo

Won

Mun

Shin

et al. 2016

Arthritis & Rheumatology

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Objective CD97, a member of the EGF-TM7 family of adhesion GPCR, is expressed on various cell types. We report here the contradictory role of CD97 in osteoclastogenesis in both basal and response to TNF treatment. We found that RANKL induced CD97 in FACS sorted osteoclast precursor cells. To elucidate the functions of CD97 in bone and inflammation, we examined the role of CD97 on osteoclastogenesis in vitro, the skeletal phenotype of CD97-deficient mice (CD97 KO), and responses to TNFα. Methods CD97 KO mouse model and TNF challenge were used to investigate the role in bone and inflammation in vivo. The effects of CD97 in bone and inflammation were assessed using histomorphometric analysis, in vitro cultures, RT-PCR and multiplex analysis of serum. Results In vitro, RANKL induced CD97 expression in bone marrow macrophages (BMM). In vivo, trabecular bone volume in the femurs of CD97 deficient female mice was increased and was associated with a decrease in osteoclast number. CD97 KO mice have reduced potential to form osteoclast-like cells (OCL) in vitro. Further, TNFα treatment augmented osteoclast formation in calvaria of CD97 KO mice in vivo by increasing the production of RANKL and other cytokines and chemokines and by reducing OPG by calvarial cells Conclusion Our findings demonstrate that CD97 is a positive regulator of OCL differentiation, influencing bone homeostasis. However, CD97 may be essential to suppress initial osteoclastogenesis in response to acute and local inflammatory stimuli.

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Section: Discussionmentioning

confidence: 97%

Contradictory Role of CD97 in Basal and Tumor Necrosis Factor–Induced Osteoclastogenesis In Vivo

Won

Mun

Shin

et al. 2016

Arthritis & Rheumatology

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“…Interestingly, treated animals exhibited thrombocytopenia associated with a significant reduction in plasma levels of LPA and a decrease in the extent of osteolytic bone lesions. 38 The role LPA in bone metastasis was further demonstrated due to its capacity of promoting tumor cell proliferation, survival, migration, and bone resorption through both an indirect action mediating cancer cell secretion of proosteoclastic cytokines (interleukin [IL]-6, IL-8, monocyte chemoattractant protein [MCP]-1, Groa) and a direct stimulation of osteoclast differentiation and bone resorption activity 38,53,54 (Figure 2). More recently, underlying mechanisms controlling platelet-derived LPA production on cancer cell stimulation has been partly elucidated.…”

Section: Platelets and Bone Metastasismentioning

confidence: 99%

“…39 Then, LPA promotes transendothelial cell migration and establishment of a disseminated tumor cell into the bone marrow. 81 LPA enhances tumor cell proliferation and induces bone resorption through a direct action on osteoclasts 54 and indirectly throughout the secretion of anti-(GM-CSF) and pro-osteoclastic factors (IL-6, IL-8, GROa) that also act directly on osteoclasts or indirectly on osteoblasts by upregulating the release of the pro-osteoclastic factor RANKL. 38,53 Figure was generated using the database of images from Servier Medical Art from Servier (http://creativecommons.org/licenses/by/3.0/fr/).…”

Section: Platelets Megakaryocytes and Metastasis 27mentioning

confidence: 99%

Metastasis: new functional implications of platelets and megakaryocytes

Leblanc

Peyruchaud

2016

Blood

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183

131

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Platelets are essential components of hemostasis. Due to a plethora of factors released on activation, platelet functions are also connected to tumor growth, notably by acting on angiogenesis. It is now well recognized that major roles of platelets in the poor outcome of cancer patients occurs during hematogenous dissemination of cancer cells. In this review, we describe recent insights into the molecular mechanisms supporting the prometastatic activity of platelets. Platelets have been shown to promote survival of circulating tumor cells (CTCs) in the bloodstream by conferring resistance to the shear stress and attack from natural killer cells. Recently, platelets were found to promote and/or maintain the state of epithelial to mesenchymal transition on CTCs through platelet secretion of transforming growth factor β in response to CTC activation. At a later stage in the metastatic process, platelets promote extravasation and establishment of metastatic cells in distant organs as observed in bone. This particular environment is also the site of hematopoiesis, megakaryocytopoiesis, and platelet production. Increasing the number of megakaryocytes (MKs) in the bone marrow results in a high bone mass phenotype and inhibits skeletal metastasis formation of prostate cancer cells. As a result of their specific location in vascular niches in the bone marrow, MK activity might contribute to the “seed and soil” suitability between CTCs and bone. In conclusion, recent findings have made a great advance in our knowledge on how platelets contribute to the metastatic dissemination of cancer cells and that may support the development of new antimetastasis therapies.

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“…Inhibition or suppression of LPAR1 promoted differentiation of osteoblasts and bone mineralization in a mouse model of autoantibody‐mediated arthritis . Lpar1 −/− mice presented significant bone defects and low bone mass, and mechanistically, bone marrow mesenchymal progenitors from Lpar1 −/− mice displayed decreased osteoblastic differentiation . By contrast, Lpar4 −/− mice showed increased trabecular bone volume, number, and thickness, and LPAR4 inhibited osteogenic differentiation of hMSCs in vitro .…”

Section: Discussionmentioning

confidence: 98%

“…LPAR1 antagonists or LPAR1 deficiency inhibited osteoclast differentiation in mice. 20 Moreover, inhibition of LPAR1 with its antagonist completely abrogates osteogenesis of human MSCs, suggesting the regulatory role of LPA in osteoblast differentiation through activation of LPAR1. 21 This is consistent to the low bone mass phenotype observed in LPAR1 null mice.…”

Section: Introductionmentioning

confidence: 97%

Lysophosphatidic acid receptor 4 regulates osteogenic and adipogenic differentiation of progenitor cells via inactivation of RhoA/ROCK1/β-catenin signaling

Xie

Wang

et al. 2019

Stem Cells

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Recent evidence revealed that lysophosphatidic acid receptor 4 (LPAR4) plays a role in osteogenesis and bone remodeling in mice. However, the molecular mechanism by which LPAR4 controls osteogenic and adipogenic differentiation of mesenchymal progenitor cells remains pending. In the current study, our data showed that Lpar4 was expressed in bone and adipose tissue and the expression increased during osteoblast and adipocyte differentiation. Lpar4 overexpression in stromal ST2 and preosteoblastic MC3T3‐E1 cells inhibited osteogenic differentiation. By contrast, Lpar4 overexpression in ST2 and mesenchymal C3H10T1/2 cells enhanced adipogenic differentiation. Conversely, depletion of endogenous Lpar4 in the progenitor cells induced osteogenic differentiation and inhibited adipogenic differentiation. Furthermore, enhanced osteoblast differentiation and alleviated fat accumulation were observed in marrow of mice after in vivo transfection of Lpar4 siRNA. Mechanism investigations revealed that LPAR4 inhibited the activation of ras homolog family member A (RhoA)/Rho‐associated kinases 1 (ROCK1) and canonical Wnt signal pathways. ROCK1 was shown to be able to activate Wnt/β‐catenin pathway. We further demonstrated that the overexpression of ROCK1 stimulated osteogenic differentiation and restrained adipogenic differentiation from stromal progenitor cells. Moreover, overexpression of ROCK1 attenuated the inhibition of osteogenic differentiation by LPAR4. The current study has provided evidences demonstrating that RhoA/ROCK1 activates β‐catenin signaling to promote osteogenic differentiation and conversely restrain adipogenic differentiation. The inactivation of RhoA/ROCK1/β‐catenin signaling is involved in LPAR4 regulation of the directional differentiation of marrow stromal progenitor cells.

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Lysophosphatidic Acid Receptor Type 1 (LPA1) Plays a Functional Role in Osteoclast Differentiation and Bone Resorption Activity

Cited by 39 publications

References 77 publications

Contradictory Role of CD97 in Basal and Tumor Necrosis Factor–Induced Osteoclastogenesis In Vivo

Contradictory Role of CD97 in Basal and Tumor Necrosis Factor–Induced Osteoclastogenesis In Vivo

Metastasis: new functional implications of platelets and megakaryocytes

Lysophosphatidic acid receptor 4 regulates osteogenic and adipogenic differentiation of progenitor cells via inactivation of RhoA/ROCK1/β-catenin signaling

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