{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T13:00:34Z","timestamp":1784725234848,"version":"3.55.0"},"reference-count":35,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2024,11,28]],"date-time":"2024-11-28T00:00:00Z","timestamp":1732752000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2022YFC2403102"],"award-info":[{"award-number":["2022YFC2403102"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2024A03J0821"],"award-info":[{"award-number":["2024A03J0821"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2022B1111080007"],"award-info":[{"award-number":["2022B1111080007"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2021A1515012480"],"award-info":[{"award-number":["2021A1515012480"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Guangzhou city school union, China","award":["2022YFC2403102"],"award-info":[{"award-number":["2022YFC2403102"]}]},{"name":"Guangzhou city school union, China","award":["2024A03J0821"],"award-info":[{"award-number":["2024A03J0821"]}]},{"name":"Guangzhou city school union, China","award":["2022B1111080007"],"award-info":[{"award-number":["2022B1111080007"]}]},{"name":"Guangzhou city school union, China","award":["2021A1515012480"],"award-info":[{"award-number":["2021A1515012480"]}]},{"name":"R&amp;D Plan Project in Key Fields of Guangdong Province, China","award":["2022YFC2403102"],"award-info":[{"award-number":["2022YFC2403102"]}]},{"name":"R&amp;D Plan Project in Key Fields of Guangdong Province, China","award":["2024A03J0821"],"award-info":[{"award-number":["2024A03J0821"]}]},{"name":"R&amp;D Plan Project in Key Fields of Guangdong Province, China","award":["2022B1111080007"],"award-info":[{"award-number":["2022B1111080007"]}]},{"name":"R&amp;D Plan Project in Key Fields of Guangdong Province, China","award":["2021A1515012480"],"award-info":[{"award-number":["2021A1515012480"]}]},{"name":"Natural Science Foundation of Guangdong Province, China","award":["2022YFC2403102"],"award-info":[{"award-number":["2022YFC2403102"]}]},{"name":"Natural Science Foundation of Guangdong Province, China","award":["2024A03J0821"],"award-info":[{"award-number":["2024A03J0821"]}]},{"name":"Natural Science Foundation of Guangdong Province, China","award":["2022B1111080007"],"award-info":[{"award-number":["2022B1111080007"]}]},{"name":"Natural Science Foundation of Guangdong Province, China","award":["2021A1515012480"],"award-info":[{"award-number":["2021A1515012480"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Bioengineering"],"abstract":"<jats:p>While TGF-\u03b23 promoted defect healing in a primate baboon skull defect model and patients, it remains unclear whether TGF-\u03b23 affects the formation of osteoclasts and bone resorption between osteogenesis and osteolysis. Analysis of the full transcriptome of hPDLSCs (human periodontal ligament stem cells) revealed that the expression of RANKL was significantly up-regulated after TGF-\u03b23 treatment during osteogenesis, which suggests its involvement in clock-controlled autophagy in bone metabolism. TRAP staining and bone resorption lacunae were used to assess the osteoclasts formed from RANKL-induced differentiated BMMs. During osteoclast differentiation, the characteristics of autophagy regulated by TGF-\u03b23 were observed in BMMs through MDC staining, transmission electron microscopy, and LC3 immunofluorescence. The expression of related genes and proteins were detected on the sixth day in mCherry-EGFP-LC3B lentivirus-transfected BMMs using RT-qPCR and WB. Finally, a trans-well co-culture system was used to evaluate the effects of osteogenic differentiated hPDLSCs treated with TGF-\u03b23 on the osteoclastic differentiation of BMMs. The results showed 10 ng\/mL of TGF-\u03b23 significantly suppressed osteoclastic differentiation and bone resorption in BMMs (p &lt; 0.05 vs. RANKL). In particular, TGF-\u03b23 augments the expression of LC3-II to stimulate autophagy, consequently restraining osteoclastic resorption. These findings provide a molecular basis and are beneficial to illustrate the potential druggability of TGF-\u03b23 in osteoporotic diseases.<\/jats:p>","DOI":"10.3390\/bioengineering11121206","type":"journal-article","created":{"date-parts":[[2024,11,28]],"date-time":"2024-11-28T09:21:23Z","timestamp":1732785683000},"page":"1206","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["TGF-\u03b23 Restrains Osteoclastic Resorption Through Autophagy"],"prefix":"10.3390","volume":"11","author":[{"given":"Hui","family":"Liao","sequence":"first","affiliation":[{"name":"State Key Laboratory of Bioactive Molecules and Drug Gability Assessment, Jinan University, No. 855 East Xingye Avenue, Guangzhou 510632, China"},{"name":"Institute of Biomedicine, Jinan University, No. 601 Huangpu Avenue West, Guangzhou 510632, China"},{"name":"Guangdong Provincial Key Laboratory of Bioengineering Medicine, Jinan University, No. 601 Huangpu Avenue West, Guangzhou 510632, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiqin","family":"Pan","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioactive Molecules and Drug Gability Assessment, Jinan University, No. 855 East Xingye Avenue, Guangzhou 510632, China"},{"name":"Institute of Biomedicine, Jinan University, No. 601 Huangpu Avenue West, Guangzhou 510632, China"},{"name":"Guangdong Provincial Key Laboratory of Bioengineering Medicine, Jinan University, No. 601 Huangpu Avenue West, Guangzhou 510632, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiming","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioactive Molecules and Drug Gability Assessment, Jinan University, No. 855 East Xingye Avenue, Guangzhou 510632, China"},{"name":"Institute of Biomedicine, Jinan University, No. 601 Huangpu Avenue West, Guangzhou 510632, China"},{"name":"Guangdong Provincial Key Laboratory of Bioengineering Medicine, Jinan University, No. 601 Huangpu Avenue West, Guangzhou 510632, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxiao","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioactive Molecules and Drug Gability Assessment, Jinan University, No. 855 East Xingye Avenue, Guangzhou 510632, China"},{"name":"Institute of Biomedicine, Jinan University, No. 601 Huangpu Avenue West, Guangzhou 510632, China"},{"name":"Guangdong Provincial Key Laboratory of Bioengineering Medicine, Jinan University, No. 601 Huangpu Avenue West, Guangzhou 510632, China"},{"name":"School of Stomatology, Jinan University, No. 601 Huangpu Avenue West, Guangzhou 510632, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiyi","family":"Huang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioactive Molecules and Drug Gability Assessment, Jinan University, No. 855 East Xingye Avenue, Guangzhou 510632, China"},{"name":"Institute of Biomedicine, Jinan University, No. 601 Huangpu Avenue West, Guangzhou 510632, China"},{"name":"Guangdong Provincial Key Laboratory of Bioengineering Medicine, Jinan University, No. 601 Huangpu Avenue West, Guangzhou 510632, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shan","family":"Ding","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioactive Molecules and Drug Gability Assessment, Jinan University, No. 855 East Xingye Avenue, Guangzhou 510632, China"},{"name":"Engineering Research Center of Artificial Organs and Materials, Department of Materials Science and Engineering, Institute of Biomedical Engineering, Jinan University, Guangzhou No. 601 Huangpu Avenue West, Guangzhou 510632, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9790-5823","authenticated-orcid":false,"given":"Qi","family":"Xiang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioactive Molecules and Drug Gability Assessment, Jinan University, No. 855 East Xingye Avenue, Guangzhou 510632, China"},{"name":"Institute of Biomedicine, Jinan University, No. 601 Huangpu Avenue West, Guangzhou 510632, China"},{"name":"Guangdong Provincial Key Laboratory of Bioengineering Medicine, Jinan University, No. 601 Huangpu Avenue West, Guangzhou 510632, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,28]]},"reference":[{"key":"ref_1","first-page":"259","article-title":"Experimental study on the transforming growth factor \u03b23 combined with dental pulp stem cells in early bone integration of implant","volume":"53","author":"Guzalinuer","year":"2018","journal-title":"Zhonghua Kou. Qiang Yi Xue Za Zhi."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2920","DOI":"10.1016\/j.actbio.2010.02.046","article-title":"Effects of TGF-\u03b23 and preculture period of osteogenic cells on the chondrogenic differentiation of rabbit marrow mesenchymal stem cells encapsulated in a bilayered hydrogel composite","volume":"6","author":"Guo","year":"2010","journal-title":"Acta Biomater."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.biomaterials.2016.01.071","article-title":"Tissue segregation restores the induction of bone formation by the mammalian transforming growth factor-\u03b23 in calvarial defects of the non-human primate Papio ursinus","volume":"86","author":"Ripamonti","year":"2016","journal-title":"Biomaterials"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/j.biomaterials.2016.07.018","article-title":"The synergistic induction of bone formation by the osteogenic proteins of the TGF-\u03b2 supergene family","volume":"104","author":"Ripamonti","year":"2016","journal-title":"Biomaterials"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1111\/jcpe.12642","article-title":"Cementogenesis and osteogenesis in periodontal tissue regeneration by recombinant human transforming growth factor-\u03b2(3): A pilot study in Papio ursinus","volume":"44","author":"Ripamonti","year":"2017","journal-title":"J. Clin. Periodontol."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Li, Y., Qiao, Z., Yu, F., Hu, H., Huang, Y., Xiang, Q., Zhang, Q., Yang, Y., and Zhao, Y. (2019). Transforming Growth Factor-\u03b23\/Chitosan Sponge (TGF-\u03b23\/CS) Facilitates Osteogenic Differentiation of Human Periodontal Ligament Stem Cells. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20204982"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1016\/j.ajps.2022.03.003","article-title":"Sequentially releasing self-healing hydrogel fabricated with TGF\u03b23-microspheres and bFGF to facilitate rat alveolar bone defect repair","volume":"17","author":"Yu","year":"2022","journal-title":"Asian J. Pharm. Sci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.cyto.2019.03.020","article-title":"Synergistic effects of recombinant Lentiviral-mediated BMP2 and TGF-beta3 on the osteogenic differentiation of rat bone marrow mesenchymal stem cells in vitro","volume":"120","author":"He","year":"2019","journal-title":"Cytokine"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Montaseri, A., Giampietri, C., Rossi, M., Riccioli, A., Del Fattore, A., and Filippini, A. (2020). The Role of Autophagy in Osteoclast Differentiation and Bone Resorption Function. Biomolecules, 10.","DOI":"10.3390\/biom10101398"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1007\/s10753-019-01111-0","article-title":"Chloroquine and 3-Methyladenine Attenuates Periodontal Inflammation and Bone Loss in Experimental Periodontitis","volume":"43","author":"He","year":"2020","journal-title":"Inflammation"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e12714","DOI":"10.1111\/cpr.12714","article-title":"Suppression of AMP-activated protein kinase reverses osteoprotegerin-induced inhibition of osteoclast differentiation by reducing autophagy","volume":"53","author":"Tong","year":"2020","journal-title":"Cell Prolif."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1485","DOI":"10.1517\/14712598.8.10.1485","article-title":"TGF-b3: A promising growth factor in engineered organogenesis","volume":"8","author":"Hao","year":"2008","journal-title":"Expert Opin. Biol. Ther."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1002\/jor.20372","article-title":"Quantitative assessment of scaffold and growth factor-mediated repair of critically sized bone defects","volume":"25","author":"Oest","year":"2007","journal-title":"J. Orthop. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/j.biochi.2019.10.008","article-title":"Autophagy mediated by JNK1 resists apoptosis through TRAF3 degradation in osteoclastogenesis","volume":"167","author":"Ke","year":"2019","journal-title":"Biochimie"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Kim, C.-J., Shin, S.-H., Kim, B.-J., Kim, C.-H., Kim, J.-H., Kang, H.-M., Park, B.-S., and Kim, I.-R. (2018). The Effects of Kaempferol-Inhibited Autophagy on Osteoclast Formation. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19010125"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"4811","DOI":"10.1172\/JCI134214","article-title":"Osteocyte necrosis triggers osteoclast-mediated bone loss through macrophage-inducible C-type lectin","volume":"130","author":"Andreev","year":"2020","journal-title":"J. Clin. Investig."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Borggaard, X.G., Pirapaharan, D.C., Delaiss\u00e9, J.-M., and S\u00f8e, K. (2020). Osteoclasts\u2019 Ability to Generate Trenches Rather Than Pits Depends on High Levels of Active Cathepsin K and Efficient Clearance of Resorption Products. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21165924"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1016\/j.devcel.2011.08.016","article-title":"Autophagy proteins regulate the secretory component of osteoclastic bone resorption","volume":"21","author":"DeSelm","year":"2011","journal-title":"Dev. Cell"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1016\/j.bone.2015.06.014","article-title":"Glucocorticoids: Dose-related effects on osteoclast formation and function via reactive oxygen species and autophagy","volume":"79","author":"Shi","year":"2015","journal-title":"Bone"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1172\/JCI66947","article-title":"Chloroquine reduces osteoclastogenesis in murine osteoporosis by preventing TRAF3 degradation","volume":"124","author":"Xiu","year":"2014","journal-title":"J. Clin. Investig."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.imlet.2018.12.003","article-title":"A dual role of TGF-\u03b2 in human osteoclast differentiation mediated by Smad1 versus Smad3 signaling","volume":"206","author":"Lee","year":"2019","journal-title":"Immunol. Lett."},{"key":"ref_22","first-page":"167","article-title":"Osteocyte TGF\u03b21-Smad2\/3 is positively associated with bone turnover parameters in subchondral bone of advanced osteoarthritis","volume":"46","author":"Dai","year":"2020","journal-title":"Int. J. Mol. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1002\/cbf.3028","article-title":"Enhancement of RANKL-induced MITF-E expression and osteoclastogenesis by TGF-\u03b2","volume":"32","author":"Asai","year":"2014","journal-title":"Cell Biochem. Funct."},{"key":"ref_24","first-page":"400","article-title":"The role of autophagy in the differentiation of osteoclasts","volume":"36","author":"Xu","year":"2016","journal-title":"Curr. Immunol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1007\/s00223-019-00575-4","article-title":"Coordination of Fusion and Trafficking of Pre-osteoclasts at the Marrow\u2013Bone Interface","volume":"105","author":"Andersen","year":"2019","journal-title":"Calcif. Tissue Int."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Kim, J.-M., Lin, C., Stavre, Z., Greenblatt, M.B., and Shim, J.-H. (2020). Osteoblast-Osteoclast Communication and Bone Homeostasis. Cells, 9.","DOI":"10.3390\/cells9092073"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e12465","DOI":"10.1111\/jpi.12465","article-title":"Biological effects of melatonin on osteoblast\/osteoclast cocultures, bone, and quality of life: Implications of a role for MT2 melatonin receptors, MEK1\/2, and MEK5 in melatonin-mediated osteoblastogenesis","volume":"64","author":"Maria","year":"2018","journal-title":"J. Pineal Res."},{"key":"ref_28","first-page":"308","article-title":"Research progress in the mechanism of action of transforming growth factor-\u03b2 in bone metabolism","volume":"26","author":"Wang","year":"2020","journal-title":"Chin. J. Osteoporos."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Zhu, S., H\u00e4ussling, V., Aspera-Werz, R.H., Chen, T., Braun, B., Weng, W., Histing, T., and Nussler, A.K. (2020). Bisphosphonates Reduce Smoking-Induced Osteoporotic-Like Alterations by Regulating RANKL\/OPG in an Osteoblast and Osteoclast Co-Culture Model. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22010053"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Cho, E., Chen, Z., Lee, J., Lee, S., and Lee, T.-H. (2019). PSTP-3,5-Me Inhibits Osteoclast Differentiation and Bone Resorption. Molecules, 24.","DOI":"10.3390\/molecules24183346"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1294","DOI":"10.1016\/j.bone.2012.03.001","article-title":"A novel library screen identifies immunosuppressors that promote osteoblast differentiation","volume":"50","author":"Darcy","year":"2012","journal-title":"Bone"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Cali\u00f2, A., Brunelli, M., Gobbo, S., Argani, P., Munari, E., Netto, G., and Martignoni, G. (2021). Cathepsin K: A Novel Diagnostic and Predictive Biomarker for Renal Tumors. Cancers, 13.","DOI":"10.3390\/cancers13102441"},{"key":"ref_33","first-page":"84","article-title":"Function of autophagy induced by mammalian target of rapamycin complex 1 in bone metabolism","volume":"47","author":"Zhu","year":"2020","journal-title":"China Acad. J. Electron. Publ. House"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"12105","DOI":"10.1002\/jcp.27071","article-title":"Autophagy plays an essential role in bone homeostasis","volume":"234","author":"Jaber","year":"2019","journal-title":"J. Cell. Physiol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2409","DOI":"10.1080\/15548627.2023.2186112","article-title":"The role of autophagy in bone metabolism and clinical significance","volume":"19","author":"Wang","year":"2023","journal-title":"Autophagy"}],"container-title":["Bioengineering"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2306-5354\/11\/12\/1206\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:41:48Z","timestamp":1760114508000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2306-5354\/11\/12\/1206"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,28]]},"references-count":35,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["bioengineering11121206"],"URL":"https:\/\/doi.org\/10.3390\/bioengineering11121206","relation":{},"ISSN":["2306-5354"],"issn-type":[{"value":"2306-5354","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,28]]}}}