PMID- 38343941 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20240213 IS - 2470-1343 (Electronic) IS - 2470-1343 (Linking) VI - 9 IP - 5 DP - 2024 Feb 6 TI - Catalpol Promotes Osseointegration of Titanium Implants under Conditions of Type 2 Diabetes via AKT/GSK3beta/FYN Pathway-Mediated NRF2 Activation. PG - 5761-5771 LID - 10.1021/acsomega.3c08518 [doi] AB - Catalpol (CA), a compound derived from the roots of Rehmannia glutinosa, is recognized for its anti-oxidative and anti-inflammatory properties. The current study aimed to evaluate the impact of CA on the osseointegration of titanium implants (TIs) in the context of type 2 diabetes and elucidate the underlying pharmacological mechanisms. MC3T3-E1 cells were incubated on the surface of titanium plates and exposed to various media for investigating osteoblast behaviors, as follows: regular medium, medium of high glucose and high lipid (HGHL) that simulates diabetic conditions, HGHL + CA medium, or HGHL + CA + LY294002 (an inhibitor of phosphoinositide 3-kinase or PI3K) medium. TIs were also surgically implanted into the femoral condyle defects in normal mice and mouse models of type 2 diabetes mellitus (T2DM). HGHL-induced oxidative stress was found to cause osteoblast dysfunction, accompanied by the inactivation of AKT/GSK3beta/FYN pathway-mediated NRF2 signaling. However, CA administration effectively mitigated HGHL-induced oxidative stress and reactivated AKT/GSK3beta/FYN/NRF2 signaling, resulting in the reversal of HGHL-induced dysfunctions in MC3T3-E1 cells, as evidenced by enhanced osteoblast adhesion, proliferation, and differentiation, as well as reduced apoptotic injury. In addition, the positive effects of CA were confirmed in vivo by enhanced osseointegration of TIs observed in mouse models of T2DM using microcomputed tomography and histological analyses. However, the pro-osteogenic effects of CA were almost completely nullified by the addition of LY294002. These findings demonstrated for the first time that CA administration ameliorates the impairment in osseointegration of TIs under conditions of T2DM via AKT/GSK3beta/FYN pathway-mediated NRF2 activation. Given its antioxidative and pro-osteogenic properties, CA administration holds promise as a reliable therapeutic strategy in the future for implant restoration in patients with T2DM. CI - (c) 2024 The Authors. Published by American Chemical Society. FAU - Zhang, Yongzhi AU - Zhang Y AUID- ORCID: 0009-0001-2051-3335 AD - Department of Endodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, No. 44-1 Wenhua Road West, Jinan, Shandong 250012, China. FAU - Zhang, Jin AU - Zhang J AD - Department of Endodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, No. 44-1 Wenhua Road West, Jinan, Shandong 250012, China. FAU - Sun, Baiyu AU - Sun B AD - Department of Prosthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, No. 44-1 Wenhua Road West, Jinan, Shandong 250012, China. FAU - Ma, Li AU - Ma L AD - Department of Health Care (Department of General Dentistry II), School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, No. 44-1 Wenhua Road West, Jinan, Shandong 250012, China. FAU - Ma, Yue AU - Ma Y AD - Department of Health Care (Department of General Dentistry II), School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, No. 44-1 Wenhua Road West, Jinan, Shandong 250012, China. LA - eng PT - Journal Article DEP - 20240125 PL - United States TA - ACS Omega JT - ACS omega JID - 101691658 PMC - PMC10851378 COIS- The authors declare no competing financial interest. EDAT- 2024/02/12 15:42 MHDA- 2024/02/12 15:43 PMCR- 2024/01/25 CRDT- 2024/02/12 04:13 PHST- 2023/10/28 00:00 [received] PHST- 2023/12/30 00:00 [revised] PHST- 2024/01/09 00:00 [accepted] PHST- 2024/02/12 15:43 [medline] PHST- 2024/02/12 15:42 [pubmed] PHST- 2024/02/12 04:13 [entrez] PHST- 2024/01/25 00:00 [pmc-release] AID - 10.1021/acsomega.3c08518 [doi] PST - epublish SO - ACS Omega. 2024 Jan 25;9(5):5761-5771. doi: 10.1021/acsomega.3c08518. eCollection 2024 Feb 6.