TSG-6 Regulates Bone Remodeling through Inhibition of Osteoblastogenesis and Osteoclast Activation - Université d'Angers Accéder directement au contenu
Article Dans Une Revue Journal of Biological Chemistry Année : 2008

TSG-6 Regulates Bone Remodeling through Inhibition of Osteoblastogenesis and Osteoclast Activation

David-J. Mahoney
  • Fonction : Auteur
Katalin Mikecz
  • Fonction : Auteur
Tariq Ali
  • Fonction : Auteur
Dafna Benayahu
  • Fonction : Auteur
Anna Plaas
  • Fonction : Auteur
Caroline-M. Milner
  • Fonction : Auteur
Anthony-J. Day
  • Fonction : Auteur
Afsie Sabokbar
  • Fonction : Auteur

Résumé

TSG-6 is an inflammation-induced protein that is produced at pathological sites, including arthritic joints. In animal models of arthritis, TSG-6 protects against joint damage; this has been attributed to its inhibitory effects on neutrophil migration and plasmin activity. Here we investigated whether TSG-6 can directly influence bone erosion. Our data reveal that TSG-6 inhibits RANKL-induced osteoclast differentiation/activation from human and murine precursor cells, where elevated dentine erosion by osteoclasts derived from TSG-6-/- mice is consistent with the very severe arthritis seen in these animals. However, the long bones from unchallenged TSG-6-/- mice were found to have higher trabecular mass than controls, suggesting that in the absence of inflammation TSG-6 has a role in bone homeostasis; we have detected expression of the TSG-6 protein in the bone marrow of unchallenged wild type mice. Furthermore, we have observed that TSG-6 can inhibit bone morphogenetic protein-2 (BMP-2)-mediated osteoblast differentiation. Interaction analysis revealed that TSG-6 binds directly to RANKL and to BMP-2 (as well as other osteogenic BMPs but not BMP-3) via composite surfaces involving its Link and CUB modules. Consistent with this, the full-length protein is required for maximal inhibition of osteoblast differentiation and osteoclast activation, although the isolated Link module retains significant activity in the latter case. We hypothesize that TSG-6 has dual roles in bone remodeling; one protective, where it inhibits RANKL-induced bone erosion in inflammatory diseases such as arthritis, and the other homeostatic, where its interactions with BMP-2 and RANKL help to balance mineralization by osteoblasts and bone resorption by osteoclasts.

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Dates et versions

hal-03261996 , version 1 (16-06-2021)

Identifiants

Citer

David-J. Mahoney, Katalin Mikecz, Tariq Ali, Guillaume Mabilleau, Dafna Benayahu, et al.. TSG-6 Regulates Bone Remodeling through Inhibition of Osteoblastogenesis and Osteoclast Activation. Journal of Biological Chemistry, 2008, 283 (38), pp.25952 - 25962. ⟨10.1074/jbc.M802138200⟩. ⟨hal-03261996⟩

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