Targeted inhibition of osteoclastogenesis reveals the pathogenesis and therapeutics of bone loss under sympathetic neurostress
© 2022. The Author(s)..
Sympathetic cues via the adrenergic signaling critically regulate bone homeostasis and contribute to neurostress-induced bone loss, but the mechanisms and therapeutics remain incompletely elucidated. Here, we reveal an osteoclastogenesis-centered functionally important osteopenic pathogenesis under sympatho-adrenergic activation with characterized microRNA response and efficient therapeutics. We discovered that osteoclastic miR-21 was tightly regulated by sympatho-adrenergic cues downstream the β2-adrenergic receptor (β2AR) signaling, critically modulated osteoclastogenesis in vivo by inhibiting programmed cell death 4 (Pdcd4), and mediated detrimental effects of both isoproterenol (ISO) and chronic variable stress (CVS) on bone. Intriguingly, without affecting osteoblastic bone formation, bone protection against ISO and CVS was sufficiently achieved by a (D-Asp8)-lipid nanoparticle-mediated targeted inhibition of osteoclastic miR-21 or by clinically relevant drugs to suppress osteoclastogenesis. Collectively, these results unravel a previously underdetermined molecular and functional paradigm that osteoclastogenesis crucially contributes to sympatho-adrenergic regulation of bone and establish multiple targeted therapeutic strategies to counteract osteopenias under stresses.
Medienart: |
E-Artikel |
---|
Erscheinungsjahr: |
2022 |
---|---|
Erschienen: |
2022 |
Enthalten in: |
Zur Gesamtaufnahme - volume:14 |
---|---|
Enthalten in: |
International journal of oral science - 14(2022), 1 vom: 01. Aug., Seite 39 |
Sprache: |
Englisch |
---|
Beteiligte Personen: |
Sui, Bingdong [VerfasserIn] |
---|
Links: |
---|
Themen: |
Adrenergic Agents |
---|
Anmerkungen: |
Date Completed 03.08.2022 Date Revised 12.09.2022 published: Electronic Citation Status MEDLINE |
---|
doi: |
10.1038/s41368-022-00193-1 |
---|
funding: |
|
---|---|
Förderinstitution / Projekttitel: |
|
PPN (Katalog-ID): |
NLM344347168 |
---|
LEADER | 01000naa a22002652 4500 | ||
---|---|---|---|
001 | NLM344347168 | ||
003 | DE-627 | ||
005 | 20231226022546.0 | ||
007 | cr uuu---uuuuu | ||
008 | 231226s2022 xx |||||o 00| ||eng c | ||
024 | 7 | |a 10.1038/s41368-022-00193-1 |2 doi | |
028 | 5 | 2 | |a pubmed24n1147.xml |
035 | |a (DE-627)NLM344347168 | ||
035 | |a (NLM)35915088 | ||
040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
041 | |a eng | ||
100 | 1 | |a Sui, Bingdong |e verfasserin |4 aut | |
245 | 1 | 0 | |a Targeted inhibition of osteoclastogenesis reveals the pathogenesis and therapeutics of bone loss under sympathetic neurostress |
264 | 1 | |c 2022 | |
336 | |a Text |b txt |2 rdacontent | ||
337 | |a ƒaComputermedien |b c |2 rdamedia | ||
338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
500 | |a Date Completed 03.08.2022 | ||
500 | |a Date Revised 12.09.2022 | ||
500 | |a published: Electronic | ||
500 | |a Citation Status MEDLINE | ||
520 | |a © 2022. The Author(s). | ||
520 | |a Sympathetic cues via the adrenergic signaling critically regulate bone homeostasis and contribute to neurostress-induced bone loss, but the mechanisms and therapeutics remain incompletely elucidated. Here, we reveal an osteoclastogenesis-centered functionally important osteopenic pathogenesis under sympatho-adrenergic activation with characterized microRNA response and efficient therapeutics. We discovered that osteoclastic miR-21 was tightly regulated by sympatho-adrenergic cues downstream the β2-adrenergic receptor (β2AR) signaling, critically modulated osteoclastogenesis in vivo by inhibiting programmed cell death 4 (Pdcd4), and mediated detrimental effects of both isoproterenol (ISO) and chronic variable stress (CVS) on bone. Intriguingly, without affecting osteoblastic bone formation, bone protection against ISO and CVS was sufficiently achieved by a (D-Asp8)-lipid nanoparticle-mediated targeted inhibition of osteoclastic miR-21 or by clinically relevant drugs to suppress osteoclastogenesis. Collectively, these results unravel a previously underdetermined molecular and functional paradigm that osteoclastogenesis crucially contributes to sympatho-adrenergic regulation of bone and establish multiple targeted therapeutic strategies to counteract osteopenias under stresses | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a Research Support, Non-U.S. Gov't | |
650 | 7 | |a Adrenergic Agents |2 NLM | |
650 | 7 | |a Apoptosis Regulatory Proteins |2 NLM | |
650 | 7 | |a Lipid Nanoparticles |2 NLM | |
650 | 7 | |a Liposomes |2 NLM | |
650 | 7 | |a MicroRNAs |2 NLM | |
650 | 7 | |a PDCD4 protein, human |2 NLM | |
650 | 7 | |a RNA-Binding Proteins |2 NLM | |
700 | 1 | |a Liu, Jin |e verfasserin |4 aut | |
700 | 1 | |a Zheng, Chenxi |e verfasserin |4 aut | |
700 | 1 | |a Dang, Lei |e verfasserin |4 aut | |
700 | 1 | |a Chen, Ji |e verfasserin |4 aut | |
700 | 1 | |a Cao, Yuan |e verfasserin |4 aut | |
700 | 1 | |a Zhang, Kaichao |e verfasserin |4 aut | |
700 | 1 | |a Liu, Lu |e verfasserin |4 aut | |
700 | 1 | |a Dang, Minyan |e verfasserin |4 aut | |
700 | 1 | |a Zhang, Liqiang |e verfasserin |4 aut | |
700 | 1 | |a Chen, Nan |e verfasserin |4 aut | |
700 | 1 | |a He, Tao |e verfasserin |4 aut | |
700 | 1 | |a Xuan, Kun |e verfasserin |4 aut | |
700 | 1 | |a Jin, Fang |e verfasserin |4 aut | |
700 | 1 | |a Zhang, Ge |e verfasserin |4 aut | |
700 | 1 | |a Jin, Yan |e verfasserin |4 aut | |
700 | 1 | |a Hu, Chenghu |e verfasserin |4 aut | |
773 | 0 | 8 | |i Enthalten in |t International journal of oral science |d 2009 |g 14(2022), 1 vom: 01. Aug., Seite 39 |w (DE-627)NLM199824665 |x 2049-3169 |7 nnns |
773 | 1 | 8 | |g volume:14 |g year:2022 |g number:1 |g day:01 |g month:08 |g pages:39 |
856 | 4 | 0 | |u http://dx.doi.org/10.1038/s41368-022-00193-1 |3 Volltext |
912 | |a GBV_USEFLAG_A | ||
912 | |a GBV_NLM | ||
951 | |a AR | ||
952 | |d 14 |j 2022 |e 1 |b 01 |c 08 |h 39 |