Local administration of low doses of exogenous BMP2 and leptin promotes ectopic bone regeneration in leptin-deficient mice

Article type: Research Article

Authors: Zheng, Zhichao^{a; b;} | Wu, Lihong^a; | Li, Zhicong^a; | Jaspers, Richard T.^b | Huang, Hairong^c | Zhang, Qing^a | Li, Zhengmao^a | Pathak, Janak L.^a; | Wu, Gang^{d; e;} | Li, Hongtao^f;

Affiliations: [a] Affiliated Stomatology Hospital of Guangzhou Medical University, Guangdong Engineering Research Center of Oral Restoration and Reconstruction, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou, China | [b] Laboratory for Myology, Department of Human Movement Sciences, Faculty of Behavioral and Movement Sciences, Amsterdam Movement Sciences, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands | [c] Perfect Crown Dental Clinic, Hangzhou, Zhejiang, China | [d] Department of Oral and Maxillofacial Surgery/Pathology, Amsterdam UMC and Academic Center for Dentistry Amsterdam (ACTA), Amsterdam Movement Science, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands | [e] Department of Oral Cell Biology, Academic Center for Dentistry Amsterdam (ACTA), University of Amsterdam and Vrije Universiteit Amsterdam, Amsterdam, The Netherlands | [f] State Key Laboratory of Respiratory Diseases, National Clinical Research Center for Respiratory Diseases, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China

Correspondence: [*] Corresponding authors: Janak L. Pathak, Affiliated Stomatology Hospital of Guangzhou Medical University, Guangdong Engineering Research Center of Oral Restoration and Reconstruction, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou, China. E-mail: j.pathak@gzhmu.edu.cn. Gang Wu,  Department of Oral and Maxillofacial Surgery/Pathology, Amsterdam UMC and Academic Center for Dentistry Amsterdam (ACTA), Amsterdam Movement Science, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands; and Department of Oral Cell Biology, Academic Center for Dentistry Amsterdam (ACTA), University of Amsterdam and Vrije Universiteit Amsterdam, Amsterdam, The Netherlands. E-mail: g.wu@acta.nl. Hongtao Li, State Key Laboratory of Respiratory Diseases, National Clinical Research Center for Respiratory Diseases, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510230, China. E-mail: hongtaolijbmx@163.com

Note: [†] These authors contributed equally to this work.

Abstract: BACKGROUND:Obesity and leptin deficiency are associated with compromised bone regeneration. OBJECTIVE:This study aims to investigate the role of locally administrated low-dose BMP2+leptin on bone regeneration in leptin-deficient obese (ob/ob) mice. METHODS:Wildtype (WT) and ob/ob mice were divided into 3 groups (4 mice/group): BMP2 (5 μg) group, BMP2+low-dose leptin (1 μg) group, and BMP2+high-dose leptin (2.5 μg) group. WT mice were used as control mice. An equal size absorbable collagen sponge was prepared by loading the BMP2 or/and leptin and implanted subcutaneously. After 19 days, samples were collected and analyzed by micro-CT and H&E staining. RESULTS:No significant difference in bone regeneration among the three groups in WT mice. Quantification of newly formed bone parameters from micro-CT and H&E staining showed that low-dose BMP2 treatment formed less new bone in ob/ob mice compared to WT. BMP2+low-dose leptin treatment substantially rescued the compromised bone regeneration in ob/ob mice up to the level in WT mice. However, the BMP2 and high dose of leptin failed to rescue the compromised bone regeneration in ob/ob mice. CONCLUSION:Our findings suggest that a combination of the low-dose BMP2 and leptin could be a strategy to promote osteogenesis in obese populations with leptin deficiency.

Keywords: Leptin deficiency, osteogenesis, bone morphogenetic protein-2 (BMP2), ob/ob mice

DOI: 10.3233/BME-211323

Journal: Bio-Medical Materials and Engineering, vol. 33, no. 4, pp. 303-313, 2022