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Papers by Florent Elefteriou

Research paper thumbnail of Involvement of sympathetic nerves in bone metastasis

Research paper thumbnail of Abstract 1172: Targeting c-Met and VEGFR2 in the stromal compartment of prostate cancer bone metastasis

Research paper thumbnail of Autonomic Innervation of the Skeleton

Primer on the Autonomic Nervous System, 2012

Research paper thumbnail of Control of Bone Remodeling by the Peripheral Sympathetic Nervous System

Calcified Tissue International, 2014

The skeleton is no longer seen as a static, isolated, and mostly structural organ. Over the last ... more The skeleton is no longer seen as a static, isolated, and mostly structural organ. Over the last two decades, a more complete picture of the multiple functions of the skeleton has emerged, and its interactions with a growing number of apparently unrelated organs have become evident. The skeleton not only reacts to mechanical loading and inflammatory, hormonal, and mineral challenges, but also acts of its own accord by secreting factors controlling the function of other tissues, including the kidney and possibly the pancreas and gonads. It is thus becoming widely recognized that it is by nature an endocrine organ, in addition to a structural organ and site of mineral storage and hematopoiesis. Consequently and by definition, bone homeostasis must be tightly regulated and integrated with the biology of other organs to maintain whole body homeostasis, and data uncovering the involvement of the central nervous system (CNS) in the control of bone remodeling support this concept. The sympathetic nervous system (SNS) represents one of the main links between the CNS and the skeleton, based on a number of anatomic, pharmacologic, and genetic studies focused on b-adrenergic receptor (bAR) signaling in bone cells. The goal of this report was to review the data supporting the role of the SNS and bAR signaling in the regulation of skeletal homeostasis.

Research paper thumbnail of Models of Bone Metastasis

Journal of Visualized Experiments, 2012

Bone metastases are a common occurrence in several malignancies, including breast, prostate, and ... more Bone metastases are a common occurrence in several malignancies, including breast, prostate, and lung. Once established in bone, tumors are responsible for significant morbidity and mortality 1 . Thus, there is a significant need to understand the molecular mechanisms controlling the establishment, growth and activity of tumors in bone. Several in vivo models have been established to study these events and each has specific benefits and limitations. The most commonly used model utilizes intracardiac inoculation of tumor cells directly into the arterial blood supply of athymic (nude) BalbC mice. This procedure can be applied to many different tumor types (including PC-3 prostate cancer, lung carcinoma, and mouse mammary fat pad tumors); however, in this manuscript we will focus on the breast cancer model, MDA-MB-231. In this model we utilize a highly bone-selective clone, originally derived in Dr. Mundy's group in San Antonio sternum (outlined in white). On the mouse's skin the sternal notch and xyphoid process serve as landmarks, and the needle is inserted slightly left of the sternum. Ventral radiographical view (B)of adult mouse leg showing proper placement of needle in the proximal tibia, aligned between Journal of Visualized Experiments

Research paper thumbnail of Inner ear vestibular signals regulate bone remodeling via the sympathetic nervous system

Journal of Bone and Mineral Research, 2014

The inner ear vestibular system has numerous projections on central brain centers that regulate s... more The inner ear vestibular system has numerous projections on central brain centers that regulate sympathetic outflow, and skeletal sympathetic projections affect bone remodeling by inhibiting bone formation by osteoblasts and promoting bone resorption by osteoclasts. In this study, we show that bilateral vestibular lesions in mice cause a low bone mass phenotype associated with decreased bone formation and increased bone resorpt ion. This reduction in bone mass is most pronounced in lower limbs, is not associated with reduced locomotor activity or chronic inflammation, and could be prevented by the administration of the β-blocker propranolol and by genetic deletion of the β2-adrenergic receptor, globally or specifically in osteoblasts. These results provide novel experimental evidence supporting a functional autonomic link between central proprioceptive vestibular structures and the skeleton. Because vestibular dysfunction often affects the elderly, these results also suggest that age-related bone loss might have a vestibular component, and that patients with inner ear pathologies might be at risk for fracture. Lastly, these data might have relevance to the bone loss observed in microgravity, as vestibular function is altered in this condition as well. This article is protected by copyright. All rights reserved.

Research paper thumbnail of Involvement of sympathetic nerves in bone metastasis

Research paper thumbnail of Abstract 1172: Targeting c-Met and VEGFR2 in the stromal compartment of prostate cancer bone metastasis

Research paper thumbnail of Autonomic Innervation of the Skeleton

Primer on the Autonomic Nervous System, 2012

Research paper thumbnail of Control of Bone Remodeling by the Peripheral Sympathetic Nervous System

Calcified Tissue International, 2014

The skeleton is no longer seen as a static, isolated, and mostly structural organ. Over the last ... more The skeleton is no longer seen as a static, isolated, and mostly structural organ. Over the last two decades, a more complete picture of the multiple functions of the skeleton has emerged, and its interactions with a growing number of apparently unrelated organs have become evident. The skeleton not only reacts to mechanical loading and inflammatory, hormonal, and mineral challenges, but also acts of its own accord by secreting factors controlling the function of other tissues, including the kidney and possibly the pancreas and gonads. It is thus becoming widely recognized that it is by nature an endocrine organ, in addition to a structural organ and site of mineral storage and hematopoiesis. Consequently and by definition, bone homeostasis must be tightly regulated and integrated with the biology of other organs to maintain whole body homeostasis, and data uncovering the involvement of the central nervous system (CNS) in the control of bone remodeling support this concept. The sympathetic nervous system (SNS) represents one of the main links between the CNS and the skeleton, based on a number of anatomic, pharmacologic, and genetic studies focused on b-adrenergic receptor (bAR) signaling in bone cells. The goal of this report was to review the data supporting the role of the SNS and bAR signaling in the regulation of skeletal homeostasis.

Research paper thumbnail of Models of Bone Metastasis

Journal of Visualized Experiments, 2012

Bone metastases are a common occurrence in several malignancies, including breast, prostate, and ... more Bone metastases are a common occurrence in several malignancies, including breast, prostate, and lung. Once established in bone, tumors are responsible for significant morbidity and mortality 1 . Thus, there is a significant need to understand the molecular mechanisms controlling the establishment, growth and activity of tumors in bone. Several in vivo models have been established to study these events and each has specific benefits and limitations. The most commonly used model utilizes intracardiac inoculation of tumor cells directly into the arterial blood supply of athymic (nude) BalbC mice. This procedure can be applied to many different tumor types (including PC-3 prostate cancer, lung carcinoma, and mouse mammary fat pad tumors); however, in this manuscript we will focus on the breast cancer model, MDA-MB-231. In this model we utilize a highly bone-selective clone, originally derived in Dr. Mundy's group in San Antonio sternum (outlined in white). On the mouse's skin the sternal notch and xyphoid process serve as landmarks, and the needle is inserted slightly left of the sternum. Ventral radiographical view (B)of adult mouse leg showing proper placement of needle in the proximal tibia, aligned between Journal of Visualized Experiments

Research paper thumbnail of Inner ear vestibular signals regulate bone remodeling via the sympathetic nervous system

Journal of Bone and Mineral Research, 2014

The inner ear vestibular system has numerous projections on central brain centers that regulate s... more The inner ear vestibular system has numerous projections on central brain centers that regulate sympathetic outflow, and skeletal sympathetic projections affect bone remodeling by inhibiting bone formation by osteoblasts and promoting bone resorption by osteoclasts. In this study, we show that bilateral vestibular lesions in mice cause a low bone mass phenotype associated with decreased bone formation and increased bone resorpt ion. This reduction in bone mass is most pronounced in lower limbs, is not associated with reduced locomotor activity or chronic inflammation, and could be prevented by the administration of the β-blocker propranolol and by genetic deletion of the β2-adrenergic receptor, globally or specifically in osteoblasts. These results provide novel experimental evidence supporting a functional autonomic link between central proprioceptive vestibular structures and the skeleton. Because vestibular dysfunction often affects the elderly, these results also suggest that age-related bone loss might have a vestibular component, and that patients with inner ear pathologies might be at risk for fracture. Lastly, these data might have relevance to the bone loss observed in microgravity, as vestibular function is altered in this condition as well. This article is protected by copyright. All rights reserved.