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Lumican Inhibits Osteoclastogenesis and Bone Resorption by Suppressing Akt Activity

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Abstract
Lumican, a ubiquitously expressed small leucine-rich proteoglycan, has been utilized in diverse biological functions. Recent experiments demonstrated that lumican stimulates preosteoblast viability and differentiation, leading to bone formation. To further understand the role of lumican in bone metabolism, we investigated its effects on osteoclast biology. Lumican inhibited both osteoclast differentiation and in vitro bone resorption in a dose-dependent manner. Consistent with this, lumican markedly decreased the expression of osteoclastogenesis markers. Moreover, the migration and fusion of preosteoclasts and the resorptive activity per osteoclast were significantly reduced in the presence of lumican, indicating that this protein affects most stages of osteoclastogenesis. Among RANKL-dependent pathways, lumican inhibited Akt but not MAP kinases such as JNK, p38, and ERK. Importantly, co-treatment with an Akt activator almost completely reversed the effect of lumican on osteoclast differentiation. Taken together, our findings revealed that lumican inhibits osteoclastogenesis by suppressing Akt activity. Thus, lumican plays an osteoprotective role by simultaneously increasing bone formation and decreasing bone resorption, suggesting that it represents a dual-action therapeutic target for osteoporosis.
Author(s)
이진영김다애김은영장은주박소정김범준
Issued Date
2021
Type
Article
Keyword
lumicanosteoclastbone resorptionAkt signaling
DOI
10.3390/ijms22094717
URI
https://oak.ulsan.ac.kr/handle/2021.oak/7912
https://ulsan-primo.hosted.exlibrisgroup.com/primo-explore/fulldisplay?docid=TN_cdi_doaj_primary_oai_doaj_org_article_67e92abc42394eb486f8554a5a05c416&context=PC&vid=ULSAN&lang=ko_KR&search_scope=default_scope&adaptor=primo_central_multiple_fe&tab=default_tab&query=any,contains,Lumican%20Inhibits%20Osteoclastogenesis%20and%20Bone%20Resorption%20by%20Suppressing%20Akt%20Activity&offset=0&pcAvailability=true
Publisher
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Location
스위스
Language
영어
ISSN
1422-0067
Citation Volume
22
Citation Number
9
Citation Start Page
0
Citation End Page
0
Appears in Collections:
Medicine > Medicine
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