Finding that osteoclasts repel osteoblast activity through Sema4D reveals novel target for bone-boosting therapies

Leah, Emma

doi:10.1038/nrrheum.2011.175

Cited by 9 publications

(10 citation statements)

References 3 publications

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“…The fact that numerous autoantibodies are detected in SLE patients, and particularly in NPSLE, as well as the association between specific autoantibodies and certain manifestations suggest that their presence is linked directly to pathogenesis [5,7,8]. More than 20 autoantibodies have been linked to NPSLE [9].…”

Section: Reviewmentioning

confidence: 99%

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Neuropsychiatric lupus: a mosaic of clinical presentations

Kivity

Agmon‐Levin

Zandman‐Goddard

et al. 2015

BMC Med

175

143

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Neuropsychiatric symptoms affect nearly half of the patients with systemic lupus erythematosus; however, the effect on disease severity, quality of life, and prognosis is tremendous. Symptoms of neuropsychiatric systemic lupus erythematosus may range from mild diffuse ones, to acute life threatening events. Although the underlying mechanisms are still largely unraveled, several pathogenic pathways are identified, such as antibody-mediated neurotoxicity, vasculopathy due to anti-phospholipid antibodies and other mechanisms, and cytokine-induced neurotoxicity. In the current review, we describe the old and the new regarding epidemiology, pathophysiology, diagnosis, and management of neuropsychiatric systemic lupus erythematosus. The possible link between neuropsychiatric symptoms and specific mechanisms may help to facilitate our understanding of the disease in the future, thus allowing for better treatment strategies.

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Section: Reviewmentioning

confidence: 99%

“…Neuropsychiatric symptoms can be among the earliest manifestations of SLE, and some reports suggest up to 40% of neuropsychiatric symptoms appear during the first year of SLE diagnosis [7]. Caucasian ethnicity and older age are associated with shorter time to neuropsychiatric damage according to the LUMINA study [35].…”

Section: Reviewmentioning

confidence: 99%

Neuropsychiatric lupus: a mosaic of clinical presentations

Kivity

Agmon‐Levin

Zandman‐Goddard

et al. 2015

BMC Med

175

143

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“…Recently, semaphorins have been targeted as new molecules that are directly implicated in cell‐cell communication pathways that occur between osteoclasts and osteoblasts . Originally depicted as axon‐guidance molecules, recent studies have demonstrated their actions outside of the nervous system, where they play key roles in cell migration, tissue development, and angiogenesis .…”

Section: Introductionmentioning

confidence: 99%

Anabolic Bone Formation Via a Site-Specific Bone-Targeting Delivery System by Interfering With Semaphorin 4d Expression

Zhang

Wei

Miron

et al. 2014

Journal of Bone and Mineral Research

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Semaphorins have been recently targeted as new molecules directly implicated in the cell-cell communication that occurs between osteoclasts and osteoblasts. Overexpression of certain semaphorins, such as semaphorin4D (sema4D), is found in an osteoporotic phenotype and plays a key role in osteoclast activity by suppressing osteoblast maturation, thus significantly altering the bone modeling cycle. In the present study, we fabricate a site-specific bone-targeting drug-delivery system from polymeric nanoparticles with the incorporation of siRNA interference molecule for sema4D and demonstrate their cellular uptake and intracellular trafficking within osteoclasts, thus preventing the suppression of osteoblast activity. We then demonstrate in an osteoporotic animal model induced by ovariectomy that weekly intravenous injections led to a significantly greater number of active osteoblasts at the bone surface, resulting in higher bone volume in compromised animals. The findings from the present study demonstrate a novel and promising site-specific therapeutic option for the treatment of osteoporosis via interference of the sema4D-plexin cell communication pathway between osteoclasts and osteoblasts.

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“…Recently, semaphorins have been targeted as molecules that are directly implicated in the cell-cell cross-talk between osteoclasts and osteoblasts 12 13 14 15 16 17 18 19 20 21 . They were originally identified as axon-guidance molecules but have since also been demonstrated to have important roles outside the nervous system.…”

Section: Discussionmentioning

confidence: 99%

“…Semaphorins have recently been targeted as molecules with osteoporosis treatment potential. They are directly implicated in the cell-cell communication between osteoclasts and osteoblasts and may be a novel target for the treatment of osteoporosis 12 13 14 15 16 17 18 19 20 21 . Furthermore, the overexpression of semaphorin4d (Sema4d) in bone tissues has been associated with osteoporosis in an animal model 22 .…”

mentioning

confidence: 99%

Bone scaffolds loaded with siRNA-Semaphorin4d for the treatment of osteoporosis related bone defects

Zhang

Wei

Miron

et al. 2016

Sci Rep

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Osteoporosis is a prominent disorder affecting over 200 million people worldwide. Recently, semaphorins have been implicated in the cell-cell communication between osteoclasts and osteoblasts and have been associated with the progression of osteoporosis. Previously, we demonstrated that knockdown of semaphorin4d (Sema4d) using siRNA delivered with a bone-targeting system prevented bone loss in an osteoporotic animal model. Here, we used this bone-specific technology containing siRNA-Sema4d and fabricated a PLLA scaffold capable of enhancing bone repair following fracture. We investigated the ability of the implant to release siRNA-Sema4d into the surrounding tissues over time and to influence new bone formation in a 3 mm femur osteoporotic defect model in ovariectomized rats. Delivery of the bone-targeting system released from PLLA scaffolds began 2 hours post-implantation, peaked at 1 day, and was sustained over a 21 day period. μCT analysis demonstrated a significantly higher bone volume/total volume bone mineral density and number of osteoblasts in the rats that were transplanted with scaffolds loaded with siRNA-Sema4d. These results confirm the specific role of Sema4d in bone remodeling and demonstrate that significant increases in the speed and quality of new bone formation occur when siRNA-Sema4d is delivered via a PLLA scaffold.

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Finding that osteoclasts repel osteoblast activity through Sema4D reveals novel target for bone-boosting therapies

Cited by 9 publications

References 3 publications

Neuropsychiatric lupus: a mosaic of clinical presentations

Neuropsychiatric lupus: a mosaic of clinical presentations

Anabolic Bone Formation Via a Site-Specific Bone-Targeting Delivery System by Interfering With Semaphorin 4d Expression

Bone scaffolds loaded with siRNA-Semaphorin4d for the treatment of osteoporosis related bone defects

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