{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T02:29:37Z","timestamp":1771468177361,"version":"3.50.1"},"reference-count":2,"publisher":"Polish Academy of Sciences Chancellery","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>This study aimed to evaluate the effects of tideglusib and bone graft mixture on bone healing. Tideglusib is a drug used in the treatment of various neurological disorders such as Alzheimer\u2019s disease. In a relevant study, the positive effect of tideglusib on the Wnt pathway, one of the pathways involved in bone regeneration and dentin tissue regeneration, was demonstrated. Dentin and bone tissues have structurally similar healing mechanisms. Therefore, tideglusib may have a similar effect on the bone tissue. The main goal of bone grafting is to provide bone regeneration and functional healing through remodeling. Bone graft materials are divided into four types based on their source: autogenous, allogenous, xenogenous, and alloplastic. Because these graft materials have various advantages and disadvantages, research continues to focus on alternative materials and applications. Sixteen New Zealand rabbits were included in this study. A unicortical 3.5 mm diameter defect was created in the tibia of rabbits under general anesthesia. The groups in the study were as follows: Group 1, left proximal tibia defect area was controlled (defect area was left empty); Group 2, left distal tibia defect area was treated with tideglusib + calcium sulfate; Group 3, right proximal tibia defect area was treated with calcium sulfate only; Group 4, right distal tibia defect area was treated with tideglusib only. Mediolateral (M\/L) radiographs of the tibia were taken on the 30th and 60th postoperative days. On the 30th day, the first eight rabbits were sacrificed, and on the 60th day, the remaining eight were sacrificed for histopathological examination. New bone formation in the obtained samples was evaluated by radiological and histopathological analyses. The study concluded that the combination of tideglusib and calcium sulfate significantly enhanced bone healing compared with the other groups (p&amp;lt;0.005). This suggests that tideglusib, either alone or in combination with bone graft materials, could serve as a promising alternative for the repair of bone defects.<\/jats:p>","DOI":"10.24425\/pjvs.2025.154940","type":"journal-article","created":{"date-parts":[[2025,6,17]],"date-time":"2025-06-17T06:57:02Z","timestamp":1750143422000},"page":"213-223","source":"Crossref","is-referenced-by-count":2,"title":["Evaluation of the effects of tideglusib and calcium sulfate on the healing of experimental bone defects in rabbits"],"prefix":"10.24425","author":[{"given":"K.","family":"Yener","sequence":"first","affiliation":[{"name":"Department of Surgery, Faculty of Veterinary Medicine, Harran University,Ak\u00e7akale Street Eyy\u00fcbiye Campus 255 AN 63200 Eyy\u00fcbiye\/\u015eanl\u0131urfa, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Hayat","sequence":"additional","affiliation":[{"name":"Department of Surgery, Faculty of Veterinary Medicine, Harran University,Ak\u00e7akale Street Eyy\u00fcbiye Campus 255 AN 63200 Eyy\u00fcbiye\/\u015eanl\u0131urfa, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"37468","published-online":{"date-parts":[[2025,1,13]]},"reference":[{"key":"#cr-split#-ref0.1","unstructured":"Amini AR, Laurencin CT, Nukavarapu SP (2012) Bone tissue engineering: recent advances and challenges. Crit Rev Biomed Eng 40: 363-408. Arioka M, Takahashi-Yanaga F, Sasaki M, Yoshihara T, Morimoto S, Hirata M, Mori Y, Sasaguri T (2014) Acceleration of bone regeneration by local application of lithium: Wnt signal-mediated osteoblastogenesis and Wnt signal-independent suppression of osteoclastogenesis. Biochem Pharmacol 90: 397-405. Audisio SA, Vaquero PG, Torres PA, Verna EC, Ocampo LN, Cristofolini AL, Merkins CI (2015) Radiological evaluation of radial bone defects treated with demineralized bone matrix in an experimental rabbit model. Bulg J Vet Med 18: 132-139. Aysan AL, \u00c7al\u0131\u015f\u0131r M, K\u0131z\u0131lda\u011f A, \u00d6zdede M, \u00d6zmen \u00d6 (2020) Effects of a glycogen synthase kinase 3 inhibitor tideglusib on bone regeneration with calvarial defects. J Craniofac Surg 31: 1477-1482. Brinker MR, O'Conner DP (2008) Basic sciences. In: Miller MD"},{"key":"#cr-split#-ref0.2","unstructured":"(ed) Review of orthopaedics. 5th ed., Saunders Elsevier, Philadelphia, pp 1-132. Bulut S, Durmu\u015f AS, K\u00f6m M, \u00c7obano\u011flu B (2001) Use of the distal portion of ulna as a segmental cortical autograft for experimentally induced fractures with large bone defect on the diaphysis of the tibia and femur in dogs. Kafkas Univ Vet Fak Derg 7: 77-85. Cavelier S, Tanzer M, Barthelat F (2020) Maximizing the strength of calcium sulfate for structural bone grafts. J Biomed Mater Res A 108: 963-971. Chen H, Cui X, Yu X, Tian XZ, Zhang BX, Tang P, Wnag Y (2010) Effects of chitosan-coated pressed calcium sulfate pellets combined with recombinant human bone morphogenetic protein 2 on bone formation in femoral condyle-contained bone defects. J Craniofac Surg 21: 188-197. Cho BC, Kim TG, Yang JD, Chung HY, Park JW, Kwon IC, Roh KH, Chung HS, Lee DS, Park NU, Kim IS (2005) Effect of calcium sulfate-chitosan composite: pellet on bone formation in bone defect. J Craniofac Surg 16: 213-224. Clevers H, Nusse R (2012) Wnt\/\u03b2-catenin signalling and disease. Cell 149: 1192-1205. Comeau-Gauthier M, Tarchala M, Luna JL, Harvey E, Merle G (2020) Unleashing \u03b2-catenin with a new anti-Alzheimer drug for bone tissue regeneration. Injury 51: 2449-2459. Cossu G, Borello U (1999) Wnt signalling and the activation of myogenesis in mammals. EMBO J 18: 6867-6872. Dom\u00ednguez JM, Fuertes A, Orozco L, del Monte-Mill\u00e1n M, Delgado E, Medina M (2012) Evidence for irreversible inhibition of glycogen synthase kinase-3\u03b2 by tideglusib. J Biol Chem 287: 893-904. Duan P, Bonewald LF (2016) The role of the Wnt\/\u03b2-catenin signaling pathway in formation and maintenance of bone and teeth. Int J Biochem Cell Biol 77: 23-29. Dumas A, Moreau MF, Gherardi RK, Basle MF, Chappard D (2009) Bone grafts cultured with bone marrow stromal cells for the repair of critical bone defects: an experimental study in mice. J Biomed Mater Res A 90: 1218-1229. Durmu\u015f AS, \u00c7eriba\u015f\u0131 AO, Can HN (2016) Effects of coral and demineralized bone matrix on bone healing. F U Sa\u011f Bil Vet Derg 30: 131-136. Efeo\u011flu C (2003) Experimental study of the application of autogenous platelet-rich plasma (PRP) and tricalcium phosphate in bone defects. Doctoral Dissertation, Ege Univ Inst Health Sci, Izmir. https:\/\/tez.yok.gov.tr\/UlusalTez Merkezi\/tezDetay.jsp?id=9ZxgRBg5STYrbRsYsWg8AQ&amp;no =0gTrNRtQzPTOLuxz8Y5J6A Emery SE, Fuller DA, Stevenson S (1996) Ceramic anterior spinal fusion: Biologic and biomechanical comparison in a canine model. Spine (Phila Pa 1976) 21: 2713-2719. Ferguson JY, Dudareva M, Riley ND, Stubbs D, Atkins BL, McNally MA (2014) The use of a biodegradable antibiotic-loaded calcium sulfate carrier containing tobramycin for the treatment of chronic osteomyelitis: a series of 195 cases. Bone Joint J 96: 829-836. Gual-Vaqu\u00e9s P, Polis-Yanes C, Estrugo-Devesa A, Ayuso-Montero R, Mar\u00ed-Roig A, L\u00f3pez-Holmen SL, Zylstra CR, Mukherjee A, Sigler RE, Faugere MC, Bouxsein ML, Deng L, Clemens TL, Williams BO (2005) Essential role of beta-catenin in postnatal bone acquisition. J Biol Chem 280: 21162-21168. \u0130yilikci B (2020) Evaluation of the effects of bone graft mixed with tideglusib on new bone formation. Specialization Thesis, Pamukkale Univ Inst Health Sci, Denizli. https:\/\/gcris.pau.edu.tr\/handle\/11499\/47881 Jiang Y, Qin H, Wan H, Yang J, Yu Q, Jiang M, Yu B (2020) Aspirin-loaded strontium-containing \u03b1-calcium sulfate hemihydrate\/nano-hydroxyapatite composite promotes regeneration of critical bone defects. J Cell Mol Med 24: 13690-13702. K\u00f6se \u0130 (2012) Experimental investigation of the effects of synthetic bone grafts, calcium channel blockers, and \u03b2-2 receptor antagonists on the healing of bone defects. Doctoral Dissertation, Dicle Univ Inst Health Sci, Diyarbak\u0131r. https:\/\/tez.yok.gov.tr\/UlusalTezMerkezi\/tezDetay.jsp?id=5i52c1o S7uzwWMSRpuugXg&amp;no=uwl-RuK6yQev3PQGnkiK9Q Lane JM, Sandhu HS (1987) Current approaches to experimental bone grafting. Orthop Clin North Am 18: 213-225. Laurencin CT, Freeman JW (2005) Ligament tissue engineering: an evolutionary materials science approach. Biomaterials 26: 7530-7536. L\u00f3pez J (2018) Autogenous teeth used for bone grafting: A systematic review. Med Oral Patol Oral Cir Bucal 23: e112-e119. Luna LG (1968) Manual of Histologic Staining Methods of the Armed Forces Institute of Pathology. 3rd ed., New York: Blakiston Division, McGraw-Hill. Martinez A, Gil C, Perez DI (2011) Glycogen synthase kinase 3 inhibitors in the next horizon for Alzheimer's disease treatment. Int J Alzheimers Dis 2011: 280502. Morvan F, Boulukos K, Lacroix-Clement P, Roman SR, Suc-Royer I, Vayssiere B, Ammann P, Martin P, Pinho S, Pognonec P, Mollat P, Niehrs C, Baron R, Rawadi G (2006) Deletion of a single allele of the Dkk1 gene leads to an increase in bone formation and bone mass. J Bone Miner Res 21: 934-945. Nandi SK, Roy S, Mukherjee P, Kundu B, De DK, Basu D (2010) Orthopaedic applications of bone graft and graft substitutes: a review. Indian J Med Res 132: 15-30. Neves VC, Babb R, Chandrasekaran D, Sharpe PT (2017) Promotion of natural tooth repair by small molecule GSK3 antagonists. Sci Rep 7: 39654. \u00d6ze\u00e7 \u0130, Yeler H (2003) Bone morphogenetic proteins and osteoinduction. Cumhuriyet Univ Dent Fac J 6: 1. https:\/\/ acikbilim.yok.gov.tr\/bitstream\/handle\/20.500.12812\/ 601075\/yokAcikBilim_396389.pdf?sequence=-1 \u00d6zkurt B, Tabak AY (2011) Metallic biomaterials and metallosis. TOTBID Review Journal 10: 83-86. Papadimitriou K, Karkavelas G, Vouros L, Kessopoulou E, Konstantinidis A (2015) Effects of local application of simvastatin on bone regeneration in femoral bone defects in rabbit. J Craniomaxillofac Surg 43: 232-237. Santana RB, Trackman PC (2006) Controlled release of fibroblast growth factor 2 stimulates bone healing in an animal model of diabetes mellitus. Int J Oral Maxillofac Implants 21: 711-718. Szponder T, Mytnik E, Jaegermann Z (2013) Use of calcium sulfate as a biomaterial in the treatment of bone fractures in rabbits - Preliminary studies. Bull Vet Inst Pulawy 57: 119-122. \u015eim\u015fek A, \u00c7akmak G, Cila E (2004) Bone grafts and bone graft substitutes. TOTBID Review Journal 3: 3-4. chrome-extension: \/\/efaidnbmnnnibpcajpcglclefindmkaj\/https:\/\/dergi.totbid.org.tr\/uploads\/pdf_75.pdf Tolosa E, Litvan I, H\u00f6glinger GU, Burn D, Lees A, Andr\u00e9s MV, G\u00f3mez-Carrillo B, Le\u00f3n T, Del Ser T (2014) A phase 2 trial of the GSK-3 inhibitor tideglusib in progressive supranuclear palsy. Mov Disord 29: 470-478. Yahav A, Kurtzman GM, Katzap M, Dudek D, Baranes D (2020) Bone regeneration: properties and clinical applications of biphasic calcium sulfate. Dent Clin North Am 64: 453-472. Yang X, Li Y, Huang Q, Yang J, Shen B, Pei F (2012) Evaluation of a biodegradable graft substitute in rabbit bone defect model. Indian J Orthop 46: 266- 273. Zhao Z, Wang G, Zhang Y, Luo W, Liu S, Zeng Z, Liu Y, Zhou Y, Zhang Y (2020) Induced membrane technique combined with antibiotic-loaded calcium sulfate-calcium phosphate composite as bone graft expander for the treatment of large infected bone defects: preliminary results of 12 cases. Ann Transl Med 8: 1081. &nbsp;"}],"container-title":["Polish Journal of Veterinary Sciences"],"original-title":[],"language":"pl","link":[{"URL":"https:\/\/journals.pan.pl\/Content\/135320\/PDF\/5%20_%20Yener.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,17]],"date-time":"2025-06-17T06:57:17Z","timestamp":1750143437000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.pan.pl\/dlibra\/publication\/154940\/edition\/135320\/content"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,13]]},"references-count":2,"URL":"https:\/\/doi.org\/10.24425\/pjvs.2025.154940","relation":{},"ISSN":["1505-1773"],"issn-type":[{"value":"1505-1773","type":"print"}],"subject":[],"published":{"date-parts":[[2025,1,13]]}}}