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- Title
Dual-Function Semaphorin 4D Released by Platelets: Suppression of Osteoblastogenesis and Promotion of Osteoclastogenesis.
- Authors
Shindo, Satoru; Savitri, Irma Josefina; Ishii, Takenobu; Ikeda, Atsushi; Pierrelus, Roodelyne; Heidari, Alireza; Okubo, Keisuke; Nakamura, Shin; Kandalam, Umadevi; Rawas-Qalaji, Mohamad; Leon, Elizabeth; Pastore, Maria Rita; Hardigan, Patrick; Kawai, Toshihisa
- Abstract
Effects of the antiosteoblastogenesis factor Semaphorin 4D (Sema4D), expressed by thrombin-activated platelets (TPs), on osteoblastogenesis, as well as osteoclastogenesis, were investigated in vitro. Intact platelets released both Sema4D and IGF-1. However, in response to stimulation with thrombin, platelets upregulated the release of Sema4D, but not IGF-1. Anti-Sema4D-neutralizing monoclonal antibody (mAb) upregulated TP-mediated osteoblastogenesis in MC3T3-E1 osteoblast precursors. MC3T3-E1 cells exposed to TPs induced phosphorylation of Akt and ERK further upregulated by the addition of anti-sema4D-mAb, suggesting the suppressive effects of TP-expressing Sema4D on osteoblastogenesis. On the other hand, TPs promoted RANKL-mediated osteoclastogenesis in the primary culture of bone-marrow-derived mononuclear cells (BMMCs). Among the known three receptors of Sema4D, including Plexin B1, Plexin B2 and CD72, little Plexin B2 was detected, and no Plexin B1 was detected, but a high level of CD72 mRNA was detected in RANKL-stimulated BMMCs by qPCR. Both anti-Sema4D-mAb and anti-CD72-mAb suppressed RANKL-induced osteoclast formation and bone resorptive activity, suggesting that Sema4D released by TPs promotes osteoclastogenesis via ligation to a CD72 receptor. This study demonstrated that Sema4D released by TPs suppresses osteogenic activity and promotes osteoclastogenesis, suggesting the novel property of platelets in bone-remodeling processes.
- Subjects
SEMAPHORINS; BONE resorption; BLOOD platelets; BONE growth; OSTEOCLASTOGENESIS; MONOCLONAL antibodies; THROMBIN
- Publication
International Journal of Molecular Sciences, 2022, Vol 23, Issue 6, p2938
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms23062938