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{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/2970902","sourcedb":"PMC","sourceid":"2970902","source_url":"https://www.ncbi.nlm.nih.gov/pmc/2970902","text":"It has previously been shown in cell culture studies on human as well as murine osteoblast cell lines and in animal models that bortezomib may induce proliferation and differentiation of osteoblast precursors and stimulate bone formation (25–30). In our in vitro model of human osteoblast precursors, we found that not only bortezomib but also glucocorticoid induced proliferation of osteoblast precursors (46). However, unlike bortezomib, which stimulated osteoblast differentiation, treatment with glucocorticoid inhibited differentiation (47, 48). The inhibition of osteoblast maturation by the glucocorticoid was found both in osteoblast precursors (reduced osteopontin) and in more mature osteoblasts (reduced collagen type I). The expression of osteopontin by osteoblast precursors and collagen type-1 by more mature osteoblasts was suppressed by the glucocorticoid in both cases to levels that were lower than the untreated control, suggesting that glucocorticoids not only inhibit differentiation, but may actually induce de-differentiation of osteoblast precursors and osteoblasts. This is probably reflected in the clinical study by a significant drop in PINP levels, indicating the loss of osteoblast maturity and capacity to form the organic bone matrix by deposition of collagen type I. The persistently elevated serum bALP in the clinical study could suggest that bALP is clinically less relevant as a marker than PINP, as bALP may just reflect proliferation of osteoblast precursors with or without the capacity to form bone.","tracks":[{"project":"MyTest","denotations":[{"id":"20528908-12782679-29035927","span":{"begin":239,"end":241},"obj":"12782679"},{"id":"20528908-18219387-29035927","span":{"begin":239,"end":241},"obj":"18219387"},{"id":"20528908-18575758-29035927","span":{"begin":239,"end":241},"obj":"18575758"},{"id":"20528908-17910634-29035927","span":{"begin":239,"end":241},"obj":"17910634"},{"id":"20528908-18980173-29035927","span":{"begin":239,"end":241},"obj":"18980173"},{"id":"20528908-19196662-29035927","span":{"begin":239,"end":241},"obj":"19196662"},{"id":"20528908-9245490-29035928","span":{"begin":407,"end":409},"obj":"9245490"},{"id":"20528908-11996905-29035929","span":{"begin":542,"end":544},"obj":"11996905"},{"id":"20528908-11344047-29035930","span":{"begin":546,"end":548},"obj":"11344047"}],"namespaces":[{"prefix":"_base","uri":"https://www.uniprot.org/uniprot/testbase"},{"prefix":"UniProtKB","uri":"https://www.uniprot.org/uniprot/"},{"prefix":"uniprot","uri":"https://www.uniprot.org/uniprotkb/"}],"attributes":[{"subj":"20528908-12782679-29035927","pred":"source","obj":"MyTest"},{"subj":"20528908-18219387-29035927","pred":"source","obj":"MyTest"},{"subj":"20528908-18575758-29035927","pred":"source","obj":"MyTest"},{"subj":"20528908-17910634-29035927","pred":"source","obj":"MyTest"},{"subj":"20528908-18980173-29035927","pred":"source","obj":"MyTest"},{"subj":"20528908-19196662-29035927","pred":"source","obj":"MyTest"},{"subj":"20528908-9245490-29035928","pred":"source","obj":"MyTest"},{"subj":"20528908-11996905-29035929","pred":"source","obj":"MyTest"},{"subj":"20528908-11344047-29035930","pred":"source","obj":"MyTest"}]},{"project":"0_colil","denotations":[{"id":"20528908-9245490-14708","span":{"begin":407,"end":409},"obj":"9245490"},{"id":"20528908-11996905-14709","span":{"begin":542,"end":544},"obj":"11996905"},{"id":"20528908-11344047-14710","span":{"begin":546,"end":548},"obj":"11344047"},{"id":"20528908-12782679-14707","span":{"begin":239,"end":241},"obj":"12782679"},{"id":"20528908-17910634-14707","span":{"begin":239,"end":241},"obj":"17910634"},{"id":"20528908-18219387-14707","span":{"begin":239,"end":241},"obj":"18219387"},{"id":"20528908-18575758-14707","span":{"begin":239,"end":241},"obj":"18575758"},{"id":"20528908-18980173-14707","span":{"begin":239,"end":241},"obj":"18980173"},{"id":"20528908-19196662-14707","span":{"begin":239,"end":241},"obj":"19196662"}],"attributes":[{"subj":"20528908-9245490-14708","pred":"source","obj":"0_colil"},{"subj":"20528908-11996905-14709","pred":"source","obj":"0_colil"},{"subj":"20528908-11344047-14710","pred":"source","obj":"0_colil"},{"subj":"20528908-12782679-14707","pred":"source","obj":"0_colil"},{"subj":"20528908-17910634-14707","pred":"source","obj":"0_colil"},{"subj":"20528908-18219387-14707","pred":"source","obj":"0_colil"},{"subj":"20528908-18575758-14707","pred":"source","obj":"0_colil"},{"subj":"20528908-18980173-14707","pred":"source","obj":"0_colil"},{"subj":"20528908-19196662-14707","pred":"source","obj":"0_colil"}]},{"project":"2_test","denotations":[{"id":"20528908-12782679-29035927","span":{"begin":239,"end":241},"obj":"12782679"},{"id":"20528908-18219387-29035927","span":{"begin":239,"end":241},"obj":"18219387"},{"id":"20528908-18575758-29035927","span":{"begin":239,"end":241},"obj":"18575758"},{"id":"20528908-17910634-29035927","span":{"begin":239,"end":241},"obj":"17910634"},{"id":"20528908-18980173-29035927","span":{"begin":239,"end":241},"obj":"18980173"},{"id":"20528908-19196662-29035927","span":{"begin":239,"end":241},"obj":"19196662"},{"id":"20528908-9245490-29035928","span":{"begin":407,"end":409},"obj":"9245490"},{"id":"20528908-11996905-29035929","span":{"begin":542,"end":544},"obj":"11996905"},{"id":"20528908-11344047-29035930","span":{"begin":546,"end":548},"obj":"11344047"}],"attributes":[{"subj":"20528908-12782679-29035927","pred":"source","obj":"2_test"},{"subj":"20528908-18219387-29035927","pred":"source","obj":"2_test"},{"subj":"20528908-18575758-29035927","pred":"source","obj":"2_test"},{"subj":"20528908-17910634-29035927","pred":"source","obj":"2_test"},{"subj":"20528908-18980173-29035927","pred":"source","obj":"2_test"},{"subj":"20528908-19196662-29035927","pred":"source","obj":"2_test"},{"subj":"20528908-9245490-29035928","pred":"source","obj":"2_test"},{"subj":"20528908-11996905-29035929","pred":"source","obj":"2_test"},{"subj":"20528908-11344047-29035930","pred":"source","obj":"2_test"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"MyTest","color":"#ec9793","default":true},{"id":"0_colil","color":"#93a8ec"},{"id":"2_test","color":"#c2ec93"}]}]}}