Evidence map›Paper›PMID 42613017›Full record

ArticleBone & joint research2026

Targeting AHNAK ameliorates osteonecrosis of the femoral head and affects adipogenic pathways involving Smad/PPARγ.

Mei-Feng Chen, Chih-Chien Hu, Yi-Min Hsiao, Pei-Heng Jiang, Yung-Heng Hsu, Chia-Yun Wu, Steve W N Ueng, Yuhan Chang

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Article in Bone & joint research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

8 authors.

Mei-Feng ChenBone and Joint Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan.ORCID 0000-0002-7170-0843
Chih-Chien HuBone and Joint Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan.ORCID 0000-0002-4209-7977
Yi-Min HsiaoBone and Joint Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan.ORCID 0000-0002-1817-0302
Pei-Heng JiangBone and Joint Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan.ORCID 0000-0003-0068-1881
Yung-Heng HsuBone and Joint Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan.ORCID 0000-0001-7391-3212
Chia-Yun WuBone and Joint Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan.ORCID 0009-0005-2550-1391
Steve W N UengBone and Joint Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan.ORCID 0000-0001-8969-7497
Yuhan ChangBone and Joint Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan.ORCID 0000-0002-7369-0300

Funding

Chang Gung Memorial HospitalNational Science and Technology Council
6 · The paper itself

Abstract

Aims: This study aimed to investigate the role of AHNAK in patients with osteonecrosis of the femoral head (ONFH) and its association with bone adipogenesis. Non-traumatic ONFH, primarily driven by steroid use and alcohol consumption, results in an imbalance between osteogenesis and adipogenesis. Understanding the function of AHNAK under ischaemic stress may help identify novel therapeutic targets for ONFH. Methods: Bone tissues from 19 ONFH patients and 15 control patients were analyzed using proteomics, enzyme-linked immunosorbent assay (ELISA), and immunofluorescence (IF). A steroid-induced ONFH mouse model and an ischaemia-mimicking in vitro model using MC3T3-E1 preosteoblasts were employed to examine AHNAK expression and function. AHNAK knockdown was performed using short hairpin RNA (shRNA) to assess its regulatory effects on adipogenic markers and Smad/PPARγ/C/EBPα signalling. Results: AHNAK expression was significantly upregulated in bone tissues of ONFH patients and in femoral heads of steroid-induced ONFH mice. This was accompanied by reduced osteocyte numbers and increased adipogenesis, as indicated by elevated perilipin 1 (PLIN1) expression. In vitro, ischaemic stress induced AHNAK and PLIN1 expression, whereas AHNAK knockdown reversed these effects and suppressed Smad1/5 phosphorylation and PPARγ activation. C/EBPα expression remained unchanged, suggesting a selective role of AHNAK in modulating the Smad/PPARγ axis during adipogenesis. Conclusion: AHNAK is a critical mediator of ischaemia-induced adipogenesis in ONFH through activation of the Smad/PPARγ signalling pathway, promoting the differentiation of preosteoblasts into adipocytes. Targeting AHNAK may offer a novel therapeutic strategy to reduce bone loss and marrow fat accumulation in ONFH, particularly in cases associated with steroids or metabolic dysfunction. Further studies are warranted to validate AHNAK as a clinical target.

Identifiers

PMID42613017
PMCPMC13485399

What Socratic holds

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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 Socratic graph.