{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T15:03:38Z","timestamp":1787238218508,"version":"build-2736575974"},"reference-count":29,"publisher":"Wiley","license":[{"start":{"date-parts":[[2018,9,12]],"date-time":"2018-09-12T00:00:00Z","timestamp":1536710400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81472113"],"award-info":[{"award-number":["81472113"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["BioMed Research International"],"published-print":{"date-parts":[[2018,9,12]]},"abstract":"<jats:p>\n                    Microbubbles magnify the acoustic pressure of low-intensity pulsed ultrasound (LIPUS) and may enhance its bioeffect for diagnostic and therapeutic purposes. This study compared the effect of this novel microbubble-mediated ultrasound (MUS) with that of the traditional LIPUS on osteogenesis and neovascularization in a rabbit model of steroid-associated osteonecrosis. We hypothesized that MUS might outweigh LIPUS on promoting osteogenesis and neovascularization in steroid-associated osteonecrosis. The bilateral femoral head necrosis was induced by lipopolysaccharide and methylprednisolone in the rabbits. The indices of bone mineral density (BMD), trabecular number, maximal loading strength, and mineral apposition rate were analyzed, demonstrating that the animal model of steroid-associated osteonecrosis was successfully established. Both the MUS group (\n                    <mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M1\">\n                      <mml:mrow>\n                        <mml:msub>\n                          <mml:mrow>\n                            <mml:mi mathvariant=\"normal\">G<\/mml:mi>\n                          <\/mml:mrow>\n                          <mml:mrow>\n                            <mml:mi mathvariant=\"normal\">M<\/mml:mi>\n                          <\/mml:mrow>\n                        <\/mml:msub>\n                      <\/mml:mrow>\n                    <\/mml:math>\n                    ) and the LIPUS group (\n                    <mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M2\">\n                      <mml:mrow>\n                        <mml:msub>\n                          <mml:mrow>\n                            <mml:mi mathvariant=\"normal\">G<\/mml:mi>\n                          <\/mml:mrow>\n                          <mml:mrow>\n                            <mml:mi mathvariant=\"normal\">L<\/mml:mi>\n                          <\/mml:mrow>\n                        <\/mml:msub>\n                      <\/mml:mrow>\n                    <\/mml:math>\n                    ) were insonated 20\u2009min daily for six weeks.\n                    <mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M3\">\n                      <mml:mrow>\n                        <mml:msub>\n                          <mml:mrow>\n                            <mml:mi mathvariant=\"normal\">G<\/mml:mi>\n                          <\/mml:mrow>\n                          <mml:mrow>\n                            <mml:mi mathvariant=\"normal\">M<\/mml:mi>\n                          <\/mml:mrow>\n                        <\/mml:msub>\n                      <\/mml:mrow>\n                    <\/mml:math>\n                    received an extra intracapsular injection of microbubbles before insonation every other day. Fluorescence bone labeling, Micro-CT Analysis, biomechanical test, quantitative real-time PCR, Western blot analysis, and histological evaluation were performed for comparing\n                    <mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M4\">\n                      <mml:mrow>\n                        <mml:msub>\n                          <mml:mrow>\n                            <mml:mi mathvariant=\"normal\">G<\/mml:mi>\n                          <\/mml:mrow>\n                          <mml:mrow>\n                            <mml:mi mathvariant=\"normal\">M<\/mml:mi>\n                          <\/mml:mrow>\n                        <\/mml:msub>\n                      <\/mml:mrow>\n                    <\/mml:math>\n                    with\n                    <mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M5\">\n                      <mml:mrow>\n                        <mml:msub>\n                          <mml:mrow>\n                            <mml:mi mathvariant=\"normal\">G<\/mml:mi>\n                          <\/mml:mrow>\n                          <mml:mrow>\n                            <mml:mi mathvariant=\"normal\">L<\/mml:mi>\n                          <\/mml:mrow>\n                        <\/mml:msub>\n                      <\/mml:mrow>\n                    <\/mml:math>\n                    . The results demonstrated a 39% higher mineral apposition rate in\n                    <mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M6\">\n                      <mml:mrow>\n                        <mml:msub>\n                          <mml:mrow>\n                            <mml:mi mathvariant=\"normal\">G<\/mml:mi>\n                          <\/mml:mrow>\n                          <mml:mrow>\n                            <mml:mi mathvariant=\"normal\">M<\/mml:mi>\n                          <\/mml:mrow>\n                        <\/mml:msub>\n                      <\/mml:mrow>\n                    <\/mml:math>\n                    compared with\n                    <mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M7\">\n                      <mml:mrow>\n                        <mml:msub>\n                          <mml:mrow>\n                            <mml:mi mathvariant=\"normal\">G<\/mml:mi>\n                          <\/mml:mrow>\n                          <mml:mrow>\n                            <mml:mi mathvariant=\"normal\">L<\/mml:mi>\n                          <\/mml:mrow>\n                        <\/mml:msub>\n                      <\/mml:mrow>\n                    <\/mml:math>\n                    . The BMD and the maximal loading strength of femoral head of\n                    <mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M8\">\n                      <mml:mrow>\n                        <mml:msub>\n                          <mml:mrow>\n                            <mml:mi mathvariant=\"normal\">G<\/mml:mi>\n                          <\/mml:mrow>\n                          <mml:mrow>\n                            <mml:mi mathvariant=\"normal\">M<\/mml:mi>\n                          <\/mml:mrow>\n                        <\/mml:msub>\n                      <\/mml:mrow>\n                    <\/mml:math>\n                    increased by 4.3% and 27.8% compared to those of\n                    <mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M9\">\n                      <mml:mrow>\n                        <mml:msub>\n                          <mml:mrow>\n                            <mml:mi mathvariant=\"normal\">G<\/mml:mi>\n                          <\/mml:mrow>\n                          <mml:mrow>\n                            <mml:mi mathvariant=\"normal\">L<\/mml:mi>\n                          <\/mml:mrow>\n                        <\/mml:msub>\n                      <\/mml:mrow>\n                    <\/mml:math>\n                    , respectively. The mRNA and protein expression of BMP-2 and VEGF were also significantly higher in\n                    <mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M10\">\n                      <mml:mrow>\n                        <mml:msub>\n                          <mml:mrow>\n                            <mml:mi mathvariant=\"normal\">G<\/mml:mi>\n                          <\/mml:mrow>\n                          <mml:mrow>\n                            <mml:mi mathvariant=\"normal\">M<\/mml:mi>\n                          <\/mml:mrow>\n                        <\/mml:msub>\n                      <\/mml:mrow>\n                    <\/mml:math>\n                    . The number of blood vessels of\n                    <mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M11\">\n                      <mml:mrow>\n                        <mml:msub>\n                          <mml:mrow>\n                            <mml:mi mathvariant=\"normal\">G<\/mml:mi>\n                          <\/mml:mrow>\n                          <mml:mrow>\n                            <mml:mi mathvariant=\"normal\">M<\/mml:mi>\n                          <\/mml:mrow>\n                        <\/mml:msub>\n                      <\/mml:mrow>\n                    <\/mml:math>\n                    was 65% greater than that of\n                    <mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M12\">\n                      <mml:mrow>\n                        <mml:msub>\n                          <mml:mrow>\n                            <mml:mi mathvariant=\"normal\">G<\/mml:mi>\n                          <\/mml:mrow>\n                          <mml:mrow>\n                            <mml:mi mathvariant=\"normal\">L<\/mml:mi>\n                          <\/mml:mrow>\n                        <\/mml:msub>\n                      <\/mml:mrow>\n                    <\/mml:math>\n                    . MUS is more potent than LIPUS in enhancing osteogenesis, neovascularization, and biomechanical strength of femoral head in the animal model of steroid-associated osteonecrosis. Without increasing the intensity of insonation or the risk of tissue damage, MUS is better for inhibiting the process of steroid-associated osteonecrosis.\n                  <\/jats:p>","DOI":"10.1155\/2018\/4606791","type":"journal-article","created":{"date-parts":[[2018,9,12]],"date-time":"2018-09-12T19:32:40Z","timestamp":1536780760000},"page":"1-11","source":"Crossref","is-referenced-by-count":9,"title":["Microbubble-Mediated Ultrasound Outweighs Low-Intensity Pulsed Ultrasound on Osteogenesis and Neovascularization in a Rabbit Model of Steroid-Associated Osteonecrosis"],"prefix":"10.1155","volume":"2018","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4764-5282","authenticated-orcid":true,"given":"Dan-Feng","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Orthopaedic Surgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Jie-fang Road 88, Hangzhou, 310009, China"},{"name":"Department of Orthopaedic Surgery, Shaoxing Central Hospital, Hua-yu Road 1, Keqiao, Shaoxing, 312030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5780-0541","authenticated-orcid":true,"given":"Guo-Xin","family":"Qu","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Jie-fang Road 88, Hangzhou, 310009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shi-Gui","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Jie-fang Road 88, Hangzhou, 310009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0595-9603","authenticated-orcid":true,"given":"Xun-Zi","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Second Affiliated Hospital, School of Medicine, Zhejiang 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