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Study Design: Study of regional variations in composition in a sample of 9 mildly to moderately degenerated human intervertebral discs.Objective: The aim of this study was to obtain proteoglycan distribution in human lumbar discs with high position resolution in the: 1) sagittal, 2) coronal, and 3) axial directions.Summary Of Background Data: Regional variation in disc proteoglycan content has only been reported in coronal sections in a small number of discs and with low spatial resolution in the sagittal direction, and has not been reported in the axial direction.Methods: Each of 9 human L2-L3 or L3-L4 lumbar discs (age, 53-56 years) were dissected into 36 to 41 specimens using a rectangular cutting die, measured for water content and analyzed for glycosaminoglycan content using the dimethylmethylene blue dye binding assay.Results: The intervertebral discs were mildly to moderately degenerated. They had glycosaminoglycan content ranging approximately 40 to 600 microg/mg dry tissue, with largest values in the nucleus and lowest in the outer anulus. In general, posterior regions had greater glycosaminoglycan content than anterior regions, although values were not as high as in the nucleus. Small variations in glycosaminoglycan content in the axial direction were observed with the largest values in the center, although this variation was small compared with radial variations. Water content results followed similar trends as glycosaminoglycan content with average values ranging from approximately 66% to 86%.Conclusions: A refined map of proteoglycan content is presented with 3 important findings. First, sagittal variations were distinct from coronal variations. Second, the proteoglycan content was not uniform across the nucleus regions. Third, some specimens had localized variations in proteoglycan and water contents suggestive of focal damage and degeneration. [ABSTRACT FROM AUTHOR]

The overall goal of this work is to define more clearly which mechanical loading conditions are associated with accelerated disc degeneration. This article briefly reviews recent studies describing the effects of mechanical loading on the metabolism of intervertebral disc cells and defines hypothetical models that provide a framework for quantitative relationships between mechanical loading and disc-cell metabolism. Disc cells respond to mechanical loading in a manner that depends on loading magnitude, frequency, and duration. On the basis of the current data, four models have been proposed to describe the effects of continuous loading on cellular metabolism: (1) on/off response, in which messenger ribonucleic acid (mRNA) transcription remains altered for the duration of loading; (2) maintenance, characterized by an initial change in mRNA levels with return to baseline levels; (3) adaptation, in which mRNA transcription is altered and remains at a new steady state; and (4) no response. In addition, five hypothetical mechanisms that describe the long-term consequences of these metabolic changes on disc-remodeling are presented. The transient nature of gene expression along with enzyme activation/inhibition is associated with changes at the protein level. The hypothetical models presented provide a framework for obtaining quantitative relationships between mechanical loading, gene expression, and changes at the compositional level; however, additional factors, such as regulatory mechanisms, must also be considered when describing disc-remodeling. A more quantitative relationship between mechanical loading effects and the metabolic response of the disc will contribute to injury prevention, facilitate more effective rehabilitation treatments, and help realize the potential of biologic and tissue engineering approaches toward disc repair. [ABSTRACT FROM AUTHOR]