{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T16:23:35Z","timestamp":1776788615452,"version":"3.51.2"},"reference-count":40,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2022,9,24]],"date-time":"2022-09-24T00:00:00Z","timestamp":1663977600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>As a widely used steroid hormone medicine, glucocorticoids have the potential to cause steroid-induced osteonecrosis of the femoral head (SONFH) due to mass or long-term use. The non-coding RNA hypothesis posits that they may contribute to the destruction and dysfunction of cartilages as a possible etiology of SONFH. MiR-30b-5p was identified as a regulatory factor in cartilage degeneration caused by methylprednisolone (MPS) exposure in our study through cell transfection. The luciferase reporter assay confirmed that miR-30b-5p was downregulated and runt-related transcription factor 2 (Runx2) was mediated by miR-30b-5p. The nobly increased expression of matrix metallopeptidase 13 (MMP13) and type X collagen (Col10a1) as Runx2 downstream genes contributed to the hypertrophic differentiation of chondrocytes, and the efficiently upregulated level of matrix metallopeptidase 9 (MMP9) may trigger chondrocyte apoptosis with MPS treatments. The cell transfection experiment revealed that miR-30b-5p inhibited chondrocyte hypertrophy and suppressed MPS-induced apoptosis. As a result, our findings showed that miR-30b-5p modulated Runx2, MMP9, MMP13, and Col10a1 expression, thereby mediating chondrocyte hypertrophic differentiation and apoptosis during the SONFH process. These findings revealed the mechanistic relationship between non-coding RNA and SONFH, providing a comprehensive understanding of SONFH and other bone diseases.<\/jats:p>","DOI":"10.3390\/ijms231911275","type":"journal-article","created":{"date-parts":[[2022,9,25]],"date-time":"2022-09-25T23:13:27Z","timestamp":1664147607000},"page":"11275","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Downregulation of miR-30b-5p Facilitates Chondrocyte Hypertrophy and Apoptosis via Targeting Runx2 in Steroid-Induced Osteonecrosis of the Femoral Head"],"prefix":"10.3390","volume":"23","author":[{"given":"Lishan","family":"Lin","sequence":"first","affiliation":[{"name":"College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yaling","family":"Yu","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kangping","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yixin","family":"Jiang","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhenlei","family":"Zhou","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1545","DOI":"10.3389\/fimmu.2019.01545","article-title":"A General Introduction to Glucocorticoid Biology","volume":"10","author":"Timmermans","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_2","first-page":"219","article-title":"Study of the circulation of the femoral head in some patients with arthritis deformans of the hip","volume":"5","author":"Pietrogrande","year":"1953","journal-title":"Reumatismo"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.gene.2018.05.091","article-title":"The pathogenesis of steroid-induced osteonecrosis of the femoral head: A systematic review of the literature","volume":"671","author":"Wang","year":"2018","journal-title":"Gene"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.1152\/physrev.00041.2015","article-title":"Non-coding RNAs in Development and Disease: Background, Mechanisms, and Therapeutic Approaches","volume":"96","author":"Beermann","year":"2016","journal-title":"Physiol. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e12418","DOI":"10.1111\/cpr.12418","article-title":"Circulating microRNA signature of steroid-induced osteonecrosis of the femoral head","volume":"51","author":"Li","year":"2018","journal-title":"Cell Prolif."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.gene.2018.01.057","article-title":"Effect of glucocorticoids on miRNA expression spectrum of rat femoral head microcirculation endothelial cells","volume":"651","author":"Yue","year":"2018","journal-title":"Gene"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.bone.2014.08.004","article-title":"MicroRNA-17\/20a inhibits glucocorticoid-induced osteoclast differentiation and function through targeting RANKL expression in osteoblast cells","volume":"68","author":"Shi","year":"2014","journal-title":"Bone"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1530\/JME-14-0314","article-title":"Glucocorticoid inhibits cell proliferation in differentiating osteoblasts by microRNA-199a targeting of WNT signaling","volume":"54","author":"Shi","year":"2015","journal-title":"J. Mol. Endocrinol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1016\/S0092-8674(00)80258-5","article-title":"Targeted disruption of Cbfa1 results in a complete lack of bone formation owing to maturational arrest of osteoblasts","volume":"89","author":"Komori","year":"1997","journal-title":"Cell"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1016\/S0092-8674(00)80259-7","article-title":"Cbfa1, a candidate gene for cleidocranial dysplasia syndrome, is essential for osteoblast differentiation and bone development","volume":"89","author":"Otto","year":"1997","journal-title":"Cell"},{"key":"ref_11","first-page":"168","article-title":"Molecular Mechanism of Runx2-Dependent Bone Development","volume":"43","author":"Komori","year":"2020","journal-title":"Mol. Cells"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Komori, T. (2019). Regulation of Proliferation, Differentiation and Functions of Osteoblasts by Runx2. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20071694"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"269","DOI":"10.22203\/eCM.v028a19","article-title":"Role and regulation of RUNX2 in osteogenesis","volume":"28","author":"Bruderer","year":"2014","journal-title":"Eur. Cells Mater."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"8695","DOI":"10.1074\/jbc.275.12.8695","article-title":"Cbfa1 is a positive regulatory factor in chondrocyte maturation","volume":"275","author":"Enomoto","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Pittayapruek, P., Meephansan, J., Prapapan, O., Komine, M., and Ohtsuki, M. (2016). Role of Matrix Metalloproteinases in Photoaging and Photocarcinogenesis. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17060868"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1083\/jcb.114.3.597","article-title":"Macromolecular organization of chicken type X collagen in vitro","volume":"114","author":"Kwan","year":"1991","journal-title":"J. Cell Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1007\/s00418-018-1640-6","article-title":"Runx2, an inducer of osteoblast and chondrocyte differentiation","volume":"149","author":"Komori","year":"2018","journal-title":"Histochem. Cell Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1016\/S8756-3282(03)00242-4","article-title":"Cyclic tensile strain and cyclic hydrostatic pressure differentially regulate expression of hypertrophic markers in primary chondrocytes","volume":"33","author":"Wong","year":"2003","journal-title":"Bone"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1007\/s10495-021-01665-1","article-title":"miR-30b-5p inhibits cancer progression and enhances cisplatin sensitivity in lung cancer through targeting LRP8","volume":"26","author":"Qiu","year":"2021","journal-title":"Apoptosis"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1038\/s41419-022-04657-4","article-title":"ATG7-enhanced impaired autophagy exacerbates acute pancreatitis by promoting regulated necrosis via the miR-30b-5p\/CAMKII pathway","volume":"13","author":"Ji","year":"2022","journal-title":"Cell Death Dis."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/j.gene.2017.05.040","article-title":"MiR-30b-5p functions as a tumor suppressor in cell proliferation, metastasis and epithelial-to-mesenchymal transition by targeting G-protein subunit \u03b1-13 in renal cell carcinoma","volume":"626","author":"Liu","year":"2017","journal-title":"Gene"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"897","DOI":"10.2147\/IJGM.S337951","article-title":"Identification and Validation of Novel Diagnostic Biomarkers for Keloid Based on GEO Database","volume":"15","author":"Nurzati","year":"2022","journal-title":"Int. J. Gen. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3015","DOI":"10.21037\/jtd.2019.07.50","article-title":"miR-30b-5p acts as a tumor suppressor microRNA in esophageal squamous cell carcinoma","volume":"11","author":"Xu","year":"2019","journal-title":"J. Thorac. Dis."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1007\/s10067-008-0861-9","article-title":"The use of bisphosphonate in the treatment of avascular necrosis: A systematic review","volume":"27","author":"Cardozo","year":"2008","journal-title":"Clin. Rheumatol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1473","DOI":"10.1056\/NEJM199205283262206","article-title":"Nontraumatic necrosis of bone (osteonecrosis)","volume":"326","author":"Mankin","year":"1992","journal-title":"N. Engl. J. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.3382\/ps\/pey474","article-title":"Endoplasmic reticulum stress affected chondrocyte apoptosis in femoral head necrosis induced by glucocorticoid in broilers","volume":"98","author":"Zhang","year":"2019","journal-title":"Poult. Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1955","DOI":"10.1042\/CS20181064","article-title":"BMSC-derived exosomes carrying microRNA-122-5p promote proliferation of osteoblasts in osteonecrosis of the femoral head","volume":"133","author":"Liao","year":"2019","journal-title":"Clin. Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1038\/s41419-020-2496-y","article-title":"CD41-deficient exosomes from non-traumatic femoral head necrosis tissues impair osteogenic differentiation and migration of mesenchymal stem cells","volume":"11","author":"Zhu","year":"2020","journal-title":"Cell Death Dis."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1729","DOI":"10.1007\/s00264-018-3956-1","article-title":"Animal models of steroid-induced osteonecrosis of the femoral head\u2014A comprehensive research review up to 2018","volume":"42","author":"Xu","year":"2018","journal-title":"Int. Orthop."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1097\/00003086-199711000-00003","article-title":"The Otto Aufranc Award. Lovastatin prevents steroid induced adipogenesis and osteonecrosis","volume":"344","author":"Cui","year":"1997","journal-title":"Clin. Orthop. Relat. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1523","DOI":"10.1007\/s00264-012-1497-6","article-title":"Effect of pentoxifylline on histopathological changes in steroid-induced osteonecrosis of femoral head: Experimental study in chicken","volume":"36","author":"Erken","year":"2012","journal-title":"Int. Orthop."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1038\/s41418-020-0602-4","article-title":"Nuclear miR-30b-5p suppresses TFEB-mediated lysosomal biogenesis and autophagy","volume":"28","author":"Guo","year":"2021","journal-title":"Cell Death Differ."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1220","DOI":"10.7150\/ijbs.67675","article-title":"Hypoxic pancreatic cancer derived exosomal miR-30b-5p promotes tumor angiogenesis by inhibiting GJA1 expression","volume":"18","author":"Chen","year":"2022","journal-title":"Int. J. Biol. Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1007\/s00441-009-0832-8","article-title":"Regulation of bone development and extracellular matrix protein genes by RUNX2","volume":"339","author":"Komori","year":"2010","journal-title":"Cell Tissue Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1016\/j.joca.2004.08.008","article-title":"Regulation of MMP-13 expression by RUNX2 and FGF2 in osteoarthritic cartilage","volume":"12","author":"Wang","year":"2004","journal-title":"Osteoarthr. Cartil."},{"key":"ref_36","first-page":"736","article-title":"Col10a1-Runx2 transgenic mice with delayed chondrocyte maturation are less susceptible to developing osteoarthritis","volume":"6","author":"Lu","year":"2014","journal-title":"Am. J. Transl. Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1016\/S0092-8674(00)81169-1","article-title":"MMP-9\/gelatinase B is a key regulator of growth plate angiogenesis and apoptosis of hypertrophic chondrocytes","volume":"93","author":"Vu","year":"1998","journal-title":"Cell"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2371","DOI":"10.1038\/s41598-017-02490-w","article-title":"Deletion of Runx2 in Articular Chondrocytes Decelerates the Progression of DMM-Induced Osteoarthritis in Adult Mice","volume":"7","author":"Liao","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"100088","DOI":"10.1016\/j.mbplus.2021.100088","article-title":"Runx2 is required for hypertrophic chondrocyte mediated degradation of cartilage matrix during endochondral ossification","volume":"12","author":"Rashid","year":"2021","journal-title":"Matrix Biol. Plus"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Zhao, X., Chang, G., Cheng, Y., and Zhou, Z. (2020). GABAA Receptor\/STEP61 Signaling Pathway May Be Involved in Emulsified Isoflurane Anesthesia in Rats. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21114078"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/19\/11275\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:38:56Z","timestamp":1760143136000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/19\/11275"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,24]]},"references-count":40,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2022,10]]}},"alternative-id":["ijms231911275"],"URL":"https:\/\/doi.org\/10.3390\/ijms231911275","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,24]]}}}