期刊
OSTEOARTHRITIS AND CARTILAGE
卷 27, 期 6, 页码 956-964出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.joca.2019.01.013
关键词
Cartilage endplate; Disc degeneration; Fourier transform infrared imaging; Nutrient transport; Nucleus pulposus cell; Low back pain
资金
- National Institutes of Health [R01 AR070198, P30 AR066262]
- UCSF
- UCSF School of Medicine
- UCSF Core Center for Musculoskeletal Biology Medicine
- National Center for Advancing Translational Sciences, National Institutes of Health, through UCSF, CTSI [UL1 TR001872]
- North American Spine Society Young Investigator Research Grant
Objective: Intradiscal biologic therapy is a promising strategy for managing intervertebral disc degeneration. However, these therapies require a rich nutrient supply, which may be limited by the transport properties of the cartilage endplate (CEP). This study investigated how fluctuations in CEP transport properties impact nutrient diffusion and disc cell survival and function. Design: Human CEP tissues harvested from six fresh cadaveric lumbar spines (38e66 years old) were placed at the open sides of diffusion chambers. Bovine nucleus pulposus (NP) cells cultured inside the chambers were nourished exclusively by nutrients diffusing through the CEP tissues. After 72 h in culture, depth-dependent NP cell viability and gene expression were measured, and related to CEP transport properties and biochemical composition determined using fluorescence recovery after photobleaching and Fourier transform infrared (FTIR) spectroscopy. Results: Solute diffusivity varied nearly 4-fold amongst the CEPs studied, and chambers with the least permeable CEPs appeared to have lower aggrecan, collagen-2, and matrix metalloproteinase-2 gene expression, as well as a significantly shorter viable distance from the CEP/nutrient interface. Increasing chamber cell density shortened the viable distance; however, this effect was lost for low-diffusivity CEPs, which suggests that these CEPs may not provide enough nutrient diffusion to satisfy cell demands. Solute diffusivity in the CEP was associated with biochemical composition: low-diffusivity CEPs had greater amounts of collagen and aggrecan, more mineral, and lower cross-link maturity. Conclusions: CEP transport properties dramatically affect NP cell survival/function. Degeneration-related CEP matrix changes could hinder the success of biologic therapies that require increased nutrient supply. (C) 2019 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
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