PXD076664

PXD076664 is an original dataset announced via ProteomeXchange.

Title	FLNB and TTC26 target ciliary hedgehog signaling to mediate extracellular matrix homeostasis of intervertebral disc in adolescent idiopathic scoliosis
Description	Variable recurrence risk and curve manifestations in adolescent idiopathic scoliosis (AIS) has been ascribed to the oligogenic effect of multiple genes. However, evidence to support this hypothesis is currently lacking. In this study, we generated mice carrying double heterozygous mutations by injecting mouse androgenic haploid embryonic stem cells with mutant Flnb and Ttc26 into oocytes. The double heterozygous mutant mice exhibited IS-like phenotypes. Combined knockdown of FLNB and TTC26 resulted in dysregulated extracellular matrix (ECM) homeostasis of intervertebral disc (IVD) consistent with the analysis of the nucleus pulposus (NP) tissues from AIS patients. In vitro evidence indicated that FLNB and TTC26 co-regulated nucleus pulposus cells ECM metabolism via the hedgehog pathway (Hh). Mechanically, TTC26 transported the protein arginine methyltransferases 7 (PRMT7) into primary cilia where PRMT7 methylates GLI family zinc finger 2 (GLI2), and FLNB imported methylated GLI2 into nucleus through direct interaction. Furthermore, deletion of Ptch1 or Sufu stimulated the Hh signaling to rescue the metabolic disorder in Flnb-/+; Ttc26-/+ discs. Overall, these results indicate that FLNB and TTC26 maintain IVD ECM hemostasis via Hh-GLI2 axis, and demonstrate that IVD may be involved the etiology of AIS.
HostingRepository	iProX
AnnounceDate	2026-04-13
AnnouncementXML	Submission_2026-04-13_01:08:28.905.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Heng Jiang
SpeciesList	scientific name: Mus musculus; NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2026-04-07 01:49:45	ID requested
⏵ 1	2026-04-13 01:08:29	announced

Dataset with its publication pending

submitter keyword: adolescent idiopathic scoliosis, oligogenic, extracellular matrix, intervertebral disc, primary cilia

Xuhui Zhou
contact affiliation	Department of Orthopedics, Changzheng Hospital, Naval Medical University
contact email	xhzhouspine@126.com
lab head
Heng Jiang
contact affiliation	Department of Orthopedics, Changzheng Hospital, Naval Medical University
contact email	jiangheng81@outlook.com
dataset submitter

iProX dataset URI