An antibody against Siglec-15 promotes bone formation and fracture healing by increasing TRAP+ mononuclear cells and PDGF-BB secretion
| Autor: | Ce Dou, Ruoxian Deng, Melissa Zarr, Xu Cao, Zengwu Shao, Gehua Zhen, Lieping Chen, Linda N. Liu, Yang Dan, Yusheng Li, Ruomei Wang, Qiaoyue Guo |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
medicine.medical_specialty
Histology QH301-705.5 Physiology Endocrinology Diabetes and Metabolism Osteoporosis Diseases Bone healing Bone resorption Article Internal medicine medicine QP1-981 Biology (General) Neutralizing antibody Endochondral ossification biology Chemistry Bone fracture respiratory system medicine.disease medicine.anatomical_structure Endocrinology Osteopetrosis Intramembranous ossification biology.protein Cortical bone |
| Zdroj: | Bone Research, Vol 9, Iss 1, Pp 1-11 (2021) Bone Research |
| ISSN: | 2095-6231 |
| Popis: | Osteoporosis (OP) is a common age-related disease characterized by a deterioration of bone mass and structure that predisposes patients to fragility fractures. Pharmaceutical therapies that promote anabolic bone formation in OP patients and OP-induced fracture are needed. We investigated whether a neutralizing antibody against Siglec-15 can simultaneously inhibit bone resorption and stimulate bone formation. We found that the multinucleation of osteoclasts was inhibited in SIGLEC-15 conditional knockout mice and mice undergoing Siglec-15 neutralizing antibody treatment. The secretion of platelet-derived growth factor-BB (PDGF-BB), the number of tartrate-resistant acid phosphatase-positive (TRAP+) mononuclear cells, and bone formation were significantly increased in the SIGLEC-15 conditional knockout mice and antibody-treated mice. The anabolic effect of the Siglec-15 neutralizing antibody on bone formation was blunted in mice with Pdgfb deleted in TRAP+ cells. These findings showed that the anabolic effect of the Siglec-15 neutralizing antibody was mediated by elevating PDGF-BB production of TRAP+ mononuclear cells. To test the therapeutic potential of the Siglec-15 neutralizing antibody, we injected the antibody in an ovariectomy-induced osteoporotic mouse model, which mimics postmenopausal osteoporosis in women, and in two fracture healing models because fracture is the most serious health consequence of osteoporosis. The Siglec-15 neutralizing antibody effectively reduced bone resorption and stimulated bone formation in estrogen deficiency-induced osteoporosis. Of note, the Siglec-15 neutralizing antibody promoted intramembranous and endochondral ossification at the damaged area of cortical bone in fracture healing mouse models. Thus, the Siglec-15 neutralizing antibody shows significant translational potential as a novel therapy for OP and bone fracture. |
| Databáze: | OpenAIRE |
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