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HCOS also exhibits heterogeneous pathological maldifferentiation in individual patients. Currently, the mechanism regulating HCOS differentiation remains unclear, and therapies are ineffective. Osteopontin (OPN) and osteocalcin (OCN) are markers of osteoblast maturation, and their expression is inhibited in HCOS. A previous study found that PLK2 inhibited TAp73 phosphorylation and consequent anti\u2010OS function of TAp73 in OS cells with enriched TAp73. TAp73 was also reported to regulate bone cell calcification. Here, OOS was found to have higher TAp73 levels and PLK2 expression than those in COS, which is correlated with HCOS maldifferentiation according to Spearman analysis and affects patient prognosis according to Kaplan\u2010Meier survival analysis. In the conventional OS cell\u2010line Saos2 and in patient\u2010derived xenograft OS (PDX\u2010OS) cells, increased PLK2 expression owing to abundant TAp73 levels affected OPN and OCN content as measured by RT\u2010PCR and Western blotting, and alizarin red staining showed that PLK2 affected calcium deposition in OS cells. In addition, PLK2 inhibition in PDX\u2010OS cells prohibited clone formation, as indicated by a clonogenic assay, and sensitized OS cells to cisplatin (CDDP) (which consequently limited proliferation), as shown by the CCK\u20108 assay. In an established PDX animal model with abundant TAp73 levels, PLK2 inhibition or CDDP treatment prevented tumor growth and prolonged median survival. The combined therapeutic effect of PLK2 inhibition with CDDP treatment was better than that of either monotherapy. These results indicate that increased PLK2 levels due to enriched TAp73 affect osteogenic differentiation and maturation and OS prognosis. In conclusion, PLK2 is a potential target for differentiation therapy of OS with enriched TAp73.<\/jats:p>","DOI":"10.1002\/cam4.3066","type":"journal-article","created":{"date-parts":[[2020,4,29]],"date-time":"2020-04-29T23:31:49Z","timestamp":1588203109000},"page":"4371-4385","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["PLK2 modulation of enriched TAp73 affects osteogenic differentiation and prognosis in human osteosarcoma"],"prefix":"10.1002","volume":"9","author":[{"given":"Wenhu","family":"Li","sequence":"first","affiliation":[{"name":"Department of Orthopedics Shaoguan First People's Hospital Affiliated to Southern Medical University Shaoguan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xianliao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Orthopedics Center Zhujiang Hospital of Southern Medical University Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinhua","family":"Xi","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics The Affiliated Yuebei People's Hospital of Shantou University Medical College Shaoguan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yufa","family":"Li","sequence":"additional","affiliation":[{"name":"The Second School of Clinical Medicine Southern Medical University Guangzhou China"},{"name":"Department of Pathology Guangdong provincial people's Hospital &amp; 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