{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T14:48:27Z","timestamp":1787755707984,"version":"build-2784847793"},"reference-count":71,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,2,3]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Synovial membrane-derived factors are implicated in arthritis-related bone changes. The route that synovial factors use to access subchondral bone and the mechanisms responsible for these bone changes remain unclear. A safety study involving intra-articular injection of bone morphogenetic protein-2 (BMP-2)\/calcium phosphate matrix (CPM) or CPM addresses these issues.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      Knee joints in 21 monkeys were injected with CPM or 1.5 or 4.5 mg\/mL BMP-2\/CPM and were evaluated at 1 and 8 weeks. Contralateral joints were injected with saline solution. Knee joints in 4 animals each were injected with 1.5 or 4.5 mg\/mL BMP-2\/CPM. Contralateral joints were injected with corresponding treatments at 8 weeks. Both joints were evaluated at 16 weeks. Harvested joints were evaluated grossly and with histomorphometry. Knee joints in 3 animals were injected with\n                      <jats:sup>125<\/jats:sup>\n                      I-labeled BMP-2\/CPM and evaluated with scintigraphy and autoradiography at 2 weeks to determine BMP-2 distribution.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      All treatments induced transient synovitis and increased capsular vascularization, observed to anastomose with metaphyseal venous sinusoids, but did not damage articular cartilage. Both treatments induced unanticipated activation of vascular-associated trabecular bone remodeling compartments (BRCs) restricted to injected knees. Bone volume increased in BMP-2\/CPM-injected knees at 8 and 16 weeks. Scintigraphy demonstrated metaphyseal\n                      <jats:sup>125<\/jats:sup>\n                      I-labeled BMP-2 localization restricted to injected knees, confirming local rather than systemic BMP-2 release. Autoradiography demonstrated that BMP-2 diffusion through articular cartilage into the metaphysis was blocked by the tidemark. The lack of marrow activation or de novo bone formation, previously reported following metaphyseal BMP-2\/CPM administration, confirmed BMP-2 and synovial-derived factors were not free in the marrow. The\n                      <jats:sup>125<\/jats:sup>\n                      I-labeled BMP-2\/CPM, observed within venous sinusoids of injected knees, confirmed the potential for capsular and metaphyseal venous portal communication.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>This study identifies a synovitis-induced venous portal circulation between the joint capsule and the metaphysis as an alternative to systemic circulation and local diffusion for synovial membrane-derived factors to reach subchondral bone. This study also identifies vascular-associated BRCs as a mechanism for arthritis-associated subchondral bone changes and provides additional support for their role in physiological trabecular bone remodeling and\/or modeling.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical Relevance:<\/jats:title>\n                    <jats:p>Inhibition of synovitis and accompanying abnormal vascularization may limit bone changes associated with arthritis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.2106\/jbjs.20.00883","type":"journal-article","created":{"date-parts":[[2020,12,14]],"date-time":"2020-12-14T15:01:12Z","timestamp":1607958072000},"page":"e8","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":4,"title":["Activation of Bone Remodeling Compartments in BMP-2-Injected Knees Supports a Local Vascular Mechanism for Arthritis-Related Bone Changes"],"prefix":"10.2106","volume":"103","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4351-1359","authenticated-orcid":false,"given":"Howard J.","family":"Seeherman","sequence":"first","affiliation":[{"name":"Orthopedic Research\/Pharmaceutical Development Consultant, Cambridge, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6904-7323","authenticated-orcid":false,"given":"X. Jian","family":"Li","sequence":"additional","affiliation":[{"name":"CBSET, Inc., Lexington, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5460-6815","authenticated-orcid":false,"given":"John M.","family":"Wozney","sequence":"additional","affiliation":[{"name":"Orthopedics and Pharmaceutical Development Consultant, Hudson, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2020,12,14]]},"reference":[{"issue":"11","key":"bib1-20250502","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1038\/nrrheum.2016.148","article-title":"Changes in the osteochondral unit during osteoarthritis: structure, function and cartilage-bone crosstalk","volume":"12","author":"Goldring","year":"2016","journal-title":"Nat Rev 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