Abstract
Narrowed intervertebral disc (IVD) space is a characteristic of IVD degeneration. EP sclerosis is associated with IVD, however the pathogenesis of EP hypertrophy is poorly understood. Here, we employed two spine instability mouse models to investigate temporal and spatial EP changes associated with IVD volume, considering them as a functional unit. We found that aberrant mechanical loading leads to accelerated ossification and hypertrophy of EP, decreased IVD volume and increased activation of TGFβ. Overexpression of active TGFβ in CED mice showed a similar phenotype of spine instability model. Administration of TGFβ Receptor I inhibitor attenuates pathologic changes of EP and prevents IVD narrowing. The aberrant activation of TGFβ resulting in EPs hypertrophy-induced IVD space narrowing provides a pharmacologic target that could have therapeutic potential to delay DDD.
Highlights
Degenerative disc disease (DDD) is one of the most common musculoskeletal disorders that is associated with disability and absenteeism from work
Caudal spine instability mouse model (CSI): the instability of caudal spine was induced by fully depth annular stab and nucleus pulposus (NP) removal of the caudal 7th–8th (C7–8) IVD12
Aberrant mechanical loading in the spine leads to narrowing of Intervertebral disc (IVD) space
Summary
Degenerative disc disease (DDD) is one of the most common musculoskeletal disorders that is associated with disability and absenteeism from work. DDD typically presents with back pain and imposes an enormous socio-economic burden, over $100 billion annually in the US alone. This cost exceeds the combined costs of stroke, respiratory infection, diabetes, coronary artery disease and rheumatoid disease[1,2]. Sclerosis of EPs change the mechanical property and impair diffusion and nutrient supply, accelerating IVD degeneration[5]. We investigated temporal and spatial EP changes resulting from mechanical stress by focusing on two spine instability mouse models. Of active TGFβin CED mice showed similar results to the spine instability model, whereas administration of TGFβReceptor I inhibitor attenuated EP and IVD volume changes.
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