Protection against arthritis by the parasitic worm product ES-62, and its drug-like small molecule analogues, is associated with inhibition of osteoclastogenesis

James Doonan, Felicity E. Lumb, Miguel A. Pineda, Anuradha Tarafdar, Jenny Crowe, Aneesah M. Khan, Colin J. Suckling, Margaret M. Harnett, William Harnett

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Abstract

The immunomodulatory actions of parasitic helminth excretory-secretory (ES) products that serendipitously protect against development of chronic inflammatory disorders are well established: however, knowledge of the interaction between ES products and the host musculoskeletal system in such diseases is limited. In this study, we have focused on ES-62, a glycoprotein secreted by the rodent filarial nematode Acanthocheilonema viteae that is immunomodulatory by virtue of covalently attached phosphorylcholine (PC) moieties, and also two synthetic drug-like PC-based small molecule analogues (SMAs) that mimic ES-62’s immunomodulatory activity. We have previously shown that each of these molecules prevents development of pathology in collagen-induced arthritis (CIA), a model of the musculoskeletal disease, rheumatoid arthritis (RA) and reflecting this, we now report that ES-62 and its SMAs, modify bone remodeling by altering bone marrow progenitors and thus impacting on osteoclastogenesis. Consistent with this, we find that these molecules inhibit functional osteoclast differentiation in vitro. Furthermore, this appears to be achieved by induction of anti-oxidant response gene expression, thereby resulting in reduction of the reactive oxygen species production that is necessary for the increased osteoclastogenesis witnessed in musculoskeletal diseases like RA.
Original languageEnglish
Article number1016
Number of pages13
JournalFrontiers in Immunology
Volume9
DOIs
Publication statusPublished - 14 May 2018

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Musculoskeletal Diseases
Phosphorylcholine
Helminths
Osteogenesis
Arthritis
Acanthocheilonema
Rheumatoid Arthritis
Musculoskeletal System
Experimental Arthritis
Bone Remodeling
Osteoclasts
Oxidants
Pharmaceutical Preparations
Rodentia
Reactive Oxygen Species
Glycoproteins
Bone Marrow
Pathology
Gene Expression
In Vitro Techniques

Keywords

  • ES-62
  • immunomodulation
  • osteoclast
  • parasitic worm
  • rheumatoid arthritis

Cite this

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title = "Protection against arthritis by the parasitic worm product ES-62, and its drug-like small molecule analogues, is associated with inhibition of osteoclastogenesis",
abstract = "The immunomodulatory actions of parasitic helminth excretory-secretory (ES) products that serendipitously protect against development of chronic inflammatory disorders are well established: however, knowledge of the interaction between ES products and the host musculoskeletal system in such diseases is limited. In this study, we have focused on ES-62, a glycoprotein secreted by the rodent filarial nematode Acanthocheilonema viteae that is immunomodulatory by virtue of covalently attached phosphorylcholine (PC) moieties, and also two synthetic drug-like PC-based small molecule analogues (SMAs) that mimic ES-62’s immunomodulatory activity. We have previously shown that each of these molecules prevents development of pathology in collagen-induced arthritis (CIA), a model of the musculoskeletal disease, rheumatoid arthritis (RA) and reflecting this, we now report that ES-62 and its SMAs, modify bone remodeling by altering bone marrow progenitors and thus impacting on osteoclastogenesis. Consistent with this, we find that these molecules inhibit functional osteoclast differentiation in vitro. Furthermore, this appears to be achieved by induction of anti-oxidant response gene expression, thereby resulting in reduction of the reactive oxygen species production that is necessary for the increased osteoclastogenesis witnessed in musculoskeletal diseases like RA.",
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Protection against arthritis by the parasitic worm product ES-62, and its drug-like small molecule analogues, is associated with inhibition of osteoclastogenesis. / Doonan, James; Lumb, Felicity E.; Pineda, Miguel A.; Tarafdar, Anuradha; Crowe, Jenny; Khan, Aneesah M.; Suckling, Colin J.; Harnett, Margaret M.; Harnett, William.

In: Frontiers in Immunology, Vol. 9, 1016, 14.05.2018.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Protection against arthritis by the parasitic worm product ES-62, and its drug-like small molecule analogues, is associated with inhibition of osteoclastogenesis

AU - Doonan, James

AU - Lumb, Felicity E.

AU - Pineda, Miguel A.

AU - Tarafdar, Anuradha

AU - Crowe, Jenny

AU - Khan, Aneesah M.

AU - Suckling, Colin J.

AU - Harnett, Margaret M.

AU - Harnett, William

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