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Current clinical drugs targeting either osteogenesis or osteoclastogenesis fail to effectively regulate cross\u2010talk, impeding efficient bone repair in osteoporosis patients. Ubiquitin\u2010specific protease 26 (USP26) is shown to coordinate OB\u2010OC cross\u2010talk by independently regulating \u03b2\u2010catenin and I\u03bab\u2010\u03b1. However, effective drugs for activating USP26 are still lacking. Here, they constructed bone homeostasis repair microcarriers (BHRC) that encapsulate\n                    <jats:italic>Usp26<\/jats:italic>\n                    mRNA\u2010loaded lipid nanoparticles (mRNA@LNP) within MMPs\u2010responsive GelMA hydrogel microspheres. These microcarriers target the osteoporotic microenvironment and regulate OB\u2010OC cross\u2010talk, thereby facilitating intervertebral fusion in osteoporotic rats. Results demonstrate that mRNA@LNP exhibits uniform particle size and high transfection efficiency, while GelMA hydrogel microspheres possess excellent biocompatibility and MMP responsiveness, providing favorable cell survival space and controllable release of mRNA@LNP. The released LNP upregulates USP26 protein expression, effectively promoting osteogenesis while suppressing osteoclast formation. In vivo experiments show that injecting BHRC into the defect site of intervertebral discs in osteoporotic rats significantly promotes tail vertebrae fusion by responding to the microenvironment and regulating cell\u2010to\u2010cell cross\u2010talk. Thus, the BHRC holds great potential in regulating osteoporotic homeostasis, particularly in challenging bone defects such as intervertebral fusion in osteoporotic environments.\n                  <\/jats:p>","DOI":"10.1002\/adhm.202402117","type":"journal-article","created":{"date-parts":[[2024,8,19]],"date-time":"2024-08-19T00:07:56Z","timestamp":1724026076000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Targeting Osteoblast\u2010Osteoclast Cross\u2010Talk Bone Homeostasis Repair Microcarriers Promotes Intervertebral Fusion in Osteoporotic Rats"],"prefix":"10.1002","volume":"13","author":[{"given":"Jiancheng","family":"Zheng","sequence":"first","affiliation":[{"name":"Department of Orthopaedics Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases Shanghai Institute of Traumatology and Orthopaedics Ruijin Hospital  197 Ruijin 2nd Road Shanghai 200025 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Affiliated Hospital of Jining Medical University  Jining City Shandong Province 272029 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangke","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases Shanghai Institute of Traumatology and Orthopaedics Ruijin Hospital  197 Ruijin 2nd Road Shanghai 200025 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changwei","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases Shanghai Institute of Traumatology and Orthopaedics Ruijin Hospital  197 Ruijin 2nd Road Shanghai 200025 P. R. 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Qi","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases Shanghai Institute of Traumatology and Orthopaedics Ruijin Hospital  197 Ruijin 2nd Road Shanghai 200025 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6938-9582","authenticated-orcid":false,"given":"Wenguo","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases Shanghai Institute of Traumatology and Orthopaedics Ruijin Hospital  197 Ruijin 2nd Road Shanghai 200025 P. R. 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