Evidence map›Paper›PMID 40797290›Full record

ArticleJournal of cellular and molecular medicine2025

Skimmianine Attenuates Osteoclast Activity by Suppressing ERp57-Driven Calcium Oscillations/Calcineurin/Nfatc1 Signalling in Postmenopausal Osteoporosis.

Yongshuang Lv, Xin Zhang, Qizhen Lu, Yi Zhou, Weiyi Wang, Maosheng Yang, Tao Yuan, Yikai Liu, Shui Sun, Ziqing Li

Abstract read
In one paragraph

Article in Journal of cellular and molecular medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Yongshuang LvDepartment of Joint Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China.
Xin ZhangDepartment of Joint Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China.
Qizhen LuDepartment of Joint Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China.
Yi ZhouDepartment of Joint Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China.
Weiyi WangDepartment of Joint Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China.
Maosheng YangDepartment of Joint Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China.
Tao YuanDepartment of Joint Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.
Yikai LiuThe Second Clinical Medical College of Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China.
Shui SunDepartment of Joint Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China.
Ziqing LiDepartment of Joint Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China.

Funding

National Natural Science Foundation of China no.82272485Shandong Provincial Natural Science Foundation no. ZR2024MH320Taishan Scholar Foundation of Shandong Province no. tsqnz20221170
6 · The paper itself

Abstract

Postmenopausal osteoporosis is primarily attributed to the hyperactivation of osteoclast-induced bone resorption. The differentiation and function of osteoclasts rely on the regulation of calcium oscillations/calcineurin/nuclear factor of activated T cells (Nfat) pathway. Therefore, the development of natural compounds that aim at the crucial regulator of the aforementioned pathway is essential for the suppression of osteoclastogenesis and its clinical application. Skimmianine (Ski), a furoquinoline alkaloid extracted from the Zanthoxylum genus, is known for its anti-inflammatory properties. Yet, its exact role in osteoclast differentiation and function remains largely undefined. Herein, we evaluate the impact of Ski on osteoclastogenesis and elucidate the molecular mechanism involved. We conducted network pharmacology and molecule structure-based pharmacokinetics analyses on Ski, followed by experimental validations on osteoclastogenesis in vitro and ovariectomy (OVX) mice model in vivo. The network pharmacology results indicated Ski's therapeutic effects predominantly influence the calcium signalling pathway by controlling cytosolic calcium concentration in response to bone resorption during osteoporosis. Pharmacokinetic analyses revealed Ski's excellent oral bioavailability. Furthermore, experimental validations revealed that Ski inhibited the formation of multinucleated osteoclasts in a concentration-dependent manner without affecting cell viability, while impeding osteoclast-related gene expression. The underlying mechanism involved the Ski-induced downregulation of calcineurin/Nfatc1 expression through modulation of ERp57-driven calcium oscillations. Micro-CT results confirmed that Ski treatment substantially curbed the progression of osteoporosis by mitigating bone loss. In conclusion, our findings indicated that Ski suppressed osteoclast formation by suppressing ERp57-driven calcium oscillations/calcineurin/Nfatc1 signalling, thus establishing Ski as a promising therapeutic alternative for osteoporosis.

Indexed as

CalcineurinCalcium SignalingNFATC Transcription FactorsOsteoclastsOsteoporosis, PostmenopausalAnimalsBone ResorptionCell DifferentiationFemaleHumansMiceOsteogenesisOvariectomyRAW 264.7 CellsSignal TransductionCalcineurinNFATC Transcription FactorsCalcium oscillationsCalcium signallingOsteoclastPostmenopausal osteoporosisProtein disulfide isomerase A3 (PDIA3/ERp57)Skimmianine (Ski)

Identifiers

PMID40797290
PMCPMC12343327

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.