SDC4 drives fibrotic remodeling of the intervertebral disc under altered spinal loading DOI Open Access
Kimheak Sao, Makarand V. Risbud

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Март 14, 2025

Alterations in physiological loading of the spine are deleterious to intervertebral disc health. The caudal region Ca3-6 that experiences increased flexion, showed degeneration young adult mice. Given role Syndecan 4 (SDC4), a cell surface heparan sulfate proteoglycan matrix catabolism and mechanosensing, we investigated if deletion could mitigate this loading-dependent phenotype. Notably, at spinal levels Ca3-6, Sdc4- KO mice did not exhibit collagen fibril fibronectin deposition NP compartment or alterations crosslinks observed wild-type Similarly, unlike mice, cells Sdc4 -KO retained transgelin (TGLN) expression absence COL X deposition, pointing preservation their notochordal characteristics. Proteomic analysis revealed tissues responded abnormal by increasing abundance proteins associated with extracellular remodeling, chondrocyte development, contractility. downregulated suggested decreased vesicle transport, autophagy-related pathway, RNA quality control regulation. proteome from dynamin-mediated endocytosis, DNA may underscore protection flexion-induced degeneration. Our study highlights important SDC4 fine-tuning cellular homeostasis production environment subjected altered loading.

Язык: Английский

Lactate metabolic coupling between the endplates and nucleus pulposus via MCT1 is essential for intervertebral disc health DOI Open Access
Maria Tsingas,

Konstantinos Tsingas,

Wujuan Zhang

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Фев. 25, 2025

During skeletal growth, there is an increased secretion of lactate by glycolytic nucleus pulposus (NP) cells the intervertebral disc. To investigate role this anion, we generated annulus fibrosus (AF) and endplate (EP) specific Mct1 cKO ( Slc16a1 Col2CreERT2 ) mice. Histological spatial transcriptomic studies indicated significant disc degeneration in , characterized NP cell loss delayed EP maturation. Metabolic assays showed that while AF were glycolytic, chondrocytes readily metabolized lactate. In cells, promoted protein, H3K18 lactylation, implying epigenetic programming. These findings suggest NP-derived promotes cartilage transdifferentiation into subchondral bone, its absence, continued glucose consumption persistent reduces availability to likely contributing tissue degeneration. This study provides first vivo evidence metabolic coupling between essential for growth health.

Язык: Английский

Процитировано

0
SDC4 drives fibrotic remodeling of the intervertebral disc under altered spinal loading DOI Open Access
Kimheak Sao, Makarand V. Risbud

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Март 14, 2025

Alterations in physiological loading of the spine are deleterious to intervertebral disc health. The caudal region Ca3-6 that experiences increased flexion, showed degeneration young adult mice. Given role Syndecan 4 (SDC4), a cell surface heparan sulfate proteoglycan matrix catabolism and mechanosensing, we investigated if deletion could mitigate this loading-dependent phenotype. Notably, at spinal levels Ca3-6, Sdc4- KO mice did not exhibit collagen fibril fibronectin deposition NP compartment or alterations crosslinks observed wild-type Similarly, unlike mice, cells Sdc4 -KO retained transgelin (TGLN) expression absence COL X deposition, pointing preservation their notochordal characteristics. Proteomic analysis revealed tissues responded abnormal by increasing abundance proteins associated with extracellular remodeling, chondrocyte development, contractility. downregulated suggested decreased vesicle transport, autophagy-related pathway, RNA quality control regulation. proteome from dynamin-mediated endocytosis, DNA may underscore protection flexion-induced degeneration. Our study highlights important SDC4 fine-tuning cellular homeostasis production environment subjected altered loading.

Язык: Английский

Процитировано

0