PMID- 30639440 OWN - NLM STAT- MEDLINE DCOM- 20190208 LR - 20190215 IS - 1872-7786 (Electronic) IS - 0009-2797 (Linking) VI - 300 DP - 2019 Feb 25 TI - Combined treatment with vitamin K2 and PTH enhanced bone formation in ovariectomized rats and increased differentiation of osteoblast in vitro. PG - 101-110 LID - S0009-2797(18)30561-1 [pii] LID - 10.1016/j.cbi.2019.01.012 [doi] AB - Osteoporosis is accompanied by insufficient osteogenic capacity. Several lines of evidence suggested that solutions to enhance osteoblastogenesis were important strategies for osteoporotic bone defect repair. This study investigated the effect of combined treatment with vitamin K2 and PTH on bone formation in calvarial bone defect in osteoporotic rats and its influence on osteoblast in vitro. Bilateral ovariectomy was used in SPF Sprague Dawley rats to generate an osteoporosis model. Subsequently, a calvarial defect model was established and all osteoporotic rats were randomly assigned to the following groups: control, VK (vitamin K2, 30 mg/kg everyday), PTH (recombinant human PTH (1-34), 60 mug/kg, three times a week) or VK + PTH (vitamin K2, 30 mg/kg everyday plus PTH, 60 mug/kg three times a week) for 8 weeks. In vitro, bone marrow-derived stem cells (BMSCs) were cultured and treated with vitamin K2, PTH or vitamin K2+PTH. ALP staining and western blot were performed to observe the influence of combined treatment on BMSCs. Bone formation within calvarial defect were assessed by serum gamma-carboxylated osteocalcin (Gla-OC), micro-CT, histological and immunofluorescent labeling. In this study, combined treatment of PTH and vitamin K2 showed positive effects on preventing bone loss in femurs in OVX rats. Combined treatment increased serum Gla-OC and promoted bone formation in osteoporotic calvarial bone defects. Immunohistochemistry showed that OCN and RUNX2 were more highly expressed in the VK + PTH group than in the control groups. In vitro studies results suggested that combined treatment with PTH and vitamin K2 increased expression of ALP, BMP2 and RUNX2 in BMSCs. Our data suggested that the combination of vitamin K2 and PTH increased differentiation of osteoblast and had a synergistic effect on bone formation in osteoporotic calvarial bone defect. CI - Copyright (c) 2019. Published by Elsevier B.V. FAU - Weng, She-Ji AU - Weng SJ AD - Department of Orthopaedic Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China. FAU - Yan, De-Yi AU - Yan DY AD - Department of Orthopaedic Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China. FAU - Gu, Li-Jun AU - Gu LJ AD - Department of Anesthesia and Critical Care, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China. FAU - Chen, Liang AU - Chen L AD - Department of Orthopaedic Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China. FAU - Xie, Zhong-Jie AU - Xie ZJ AD - Department of Orthopaedic Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China. FAU - Wu, Zong-Yi AU - Wu ZY AD - Department of Orthopaedic Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China. FAU - Tang, Jia-Hao AU - Tang JH AD - Department of Orthopaedic Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China. FAU - Shen, Zi-Jian AU - Shen ZJ AD - Department of Orthopaedic Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China. FAU - Li, Hang AU - Li H AD - Department of Orthopaedic Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China. FAU - Bai, Bing-Li AU - Bai BL AD - Department of Orthopaedic Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China. FAU - Boodhun, Viraj AU - Boodhun V AD - Department of Orthopaedic Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China. FAU - Yang, Lei AU - Yang L AD - Department of Orthopaedic Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China. Electronic address: 1198276989@qq.com. LA - eng PT - Journal Article DEP - 20190110 PL - Ireland TA - Chem Biol Interact JT - Chemico-biological interactions JID - 0227276 RN - 0 (Biomarkers) RN - 0 (CTX-I peptide, rat) RN - 0 (Collagen Type I) RN - 0 (Core Binding Factor Alpha 1 Subunit) RN - 0 (Parathyroid Hormone) RN - 0 (Peptide Fragments) RN - 0 (Recombinant Proteins) RN - 0 (Runx2 protein, rat) RN - 104982-03-8 (Osteocalcin) RN - 11032-49-8 (Vitamin K 2) SB - IM MH - Animals MH - Biomarkers/blood MH - Bone Marrow Cells/cytology MH - Cell Differentiation/*drug effects MH - Collagen Type I/blood MH - Core Binding Factor Alpha 1 Subunit/metabolism MH - Female MH - Femur/diagnostic imaging/metabolism/pathology MH - Humans MH - Osteoblasts/cytology/drug effects/metabolism MH - Osteocalcin/metabolism MH - Osteogenesis/*drug effects MH - Ovariectomy MH - Parathyroid Hormone/genetics/metabolism/*pharmacology MH - Peptide Fragments/blood MH - Rats MH - Rats, Sprague-Dawley MH - Recombinant Proteins/biosynthesis/isolation & purification/pharmacology MH - Stem Cells/cytology/drug effects/metabolism MH - Vitamin K 2/*pharmacology MH - X-Ray Microtomography OTO - NOTNLM OT - Osteoblast OT - Osteogenesis OT - Osteoporosis OT - PTH OT - Vitamin K2 EDAT- 2019/01/15 06:00 MHDA- 2019/02/09 06:00 CRDT- 2019/01/15 06:00 PHST- 2018/04/27 00:00 [received] PHST- 2018/12/22 00:00 [revised] PHST- 2019/01/09 00:00 [accepted] PHST- 2019/01/15 06:00 [pubmed] PHST- 2019/02/09 06:00 [medline] PHST- 2019/01/15 06:00 [entrez] AID - S0009-2797(18)30561-1 [pii] AID - 10.1016/j.cbi.2019.01.012 [doi] PST - ppublish SO - Chem Biol Interact. 2019 Feb 25;300:101-110. doi: 10.1016/j.cbi.2019.01.012. Epub 2019 Jan 10.