PMID- 35328359 OWN - NLM STAT- MEDLINE DCOM- 20220408 LR - 20220408 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 23 IP - 6 DP - 2022 Mar 9 TI - Dual-Function Semaphorin 4D Released by Platelets: Suppression of Osteoblastogenesis and Promotion of Osteoclastogenesis. LID - 10.3390/ijms23062938 [doi] LID - 2938 AB - 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. FAU - Shindo, Satoru AU - Shindo S AD - Department of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University, 3200 South University Drive, Fort Lauderdale, FL 33328, USA. FAU - Savitri, Irma Josefina AU - Savitri IJ AUID- ORCID: 0000-0002-5847-6509 AD - Periodontic Department, Faculty of Dental Medicine, Universitas Airlangga, Surabaya 60132, Indonesia. FAU - Ishii, Takenobu AU - Ishii T AD - Department of Orthodontics, Tokyo Dental College, Tokyo 101-0061, Japan. FAU - Ikeda, Atsushi AU - Ikeda A AD - Department of Periodontics and Endodontics, Okayama University Hospital, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8525, Japan. FAU - Pierrelus, Roodelyne AU - Pierrelus R AD - Department of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University, 3200 South University Drive, Fort Lauderdale, FL 33328, USA. FAU - Heidari, Alireza AU - Heidari A AD - Department of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University, 3200 South University Drive, Fort Lauderdale, FL 33328, USA. FAU - Okubo, Keisuke AU - Okubo K AD - Department of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University, 3200 South University Drive, Fort Lauderdale, FL 33328, USA. FAU - Nakamura, Shin AU - Nakamura S AD - Department of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University, 3200 South University Drive, Fort Lauderdale, FL 33328, USA. FAU - Kandalam, Umadevi AU - Kandalam U AD - Woody L. Hunt School of Dental Medicine, Texas Tech University Health Sciences Center El Paso, El Paso, TX 79905, USA. FAU - Rawas-Qalaji, Mohamad AU - Rawas-Qalaji M AD - Department of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University, 3200 South University Drive, Fort Lauderdale, FL 33328, USA. FAU - Leon, Elizabeth AU - Leon E AD - Department of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University, 3200 South University Drive, Fort Lauderdale, FL 33328, USA. FAU - Pastore, Maria Rita AU - Pastore MR AD - Department of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University, 3200 South University Drive, Fort Lauderdale, FL 33328, USA. FAU - Hardigan, Patrick AU - Hardigan P AD - Dr. Kiran C. Patel College of Allopathic Medicine, Nova Southeastern University, 3200 South University Drive, Fort Lauderdale, FL 33328, USA. FAU - Kawai, Toshihisa AU - Kawai T AD - Department of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University, 3200 South University Drive, Fort Lauderdale, FL 33328, USA. LA - eng GR - DE029709/DE/NIDCR NIH HHS/United States GR - DE028715/DE/NIDCR NIH HHS/United States GR - DE027851/DE/NIDCR NIH HHS/United States GR - R21 DE028715/DE/NIDCR NIH HHS/United States GR - R01 DE029709/DE/NIDCR NIH HHS/United States GR - R15 DE027851/DE/NIDCR NIH HHS/United States PT - Journal Article DEP - 20220309 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Antigens, CD) RN - 0 (CD100 antigen) RN - 0 (Nerve Tissue Proteins) RN - 0 (Receptors, Cell Surface) RN - 0 (Semaphorins) RN - EC 3.4.21.5 (Thrombin) SB - IM MH - Antigens, CD MH - Blood Platelets MH - Nerve Tissue Proteins/genetics MH - *Osteogenesis MH - Receptors, Cell Surface/genetics MH - *Semaphorins/genetics/pharmacology MH - Thrombin/pharmacology PMC - PMC8955605 OTO - NOTNLM OT - bone regeneration OT - osteoblasts OT - osteoclasts OT - platelets OT - semaphorin 4D COIS- The authors declare no conflict of interest. EDAT- 2022/03/26 06:00 MHDA- 2022/04/09 06:00 PMCR- 2022/03/09 CRDT- 2022/03/25 01:06 PHST- 2022/01/29 00:00 [received] PHST- 2022/03/02 00:00 [revised] PHST- 2022/03/03 00:00 [accepted] PHST- 2022/03/25 01:06 [entrez] PHST- 2022/03/26 06:00 [pubmed] PHST- 2022/04/09 06:00 [medline] PHST- 2022/03/09 00:00 [pmc-release] AID - ijms23062938 [pii] AID - ijms-23-02938 [pii] AID - 10.3390/ijms23062938 [doi] PST - epublish SO - Int J Mol Sci. 2022 Mar 9;23(6):2938. doi: 10.3390/ijms23062938.