Absence of Biglycan Accelerates the Degenerative Process in Mouse Intervertebral Disc

Abstract

Study Design A study of the morphometrical and histological changes of the intervertebral discs (IVDs) in biglycan (Bgn)-deficient mice. Objective In this study we investigate whether the absence of Bgn accelerates the degenerative process in mouse IVD. Summary of Background Data Proteoglycans and collagen fibrils are major components in the extracellular matrix (ECM) composition of IVD. The ECM of IVD contains several members of the small leucine repeat proteoglycans (SLRPs) family. Bgn is one member of SLRPs family, and showed a unique expression with age and degeneration in the human IVD. To date there have been no in vivo studies to see if SLRPs have a role in maintaining the structural integrity of IVD. To explore the functions of Bgn in the IVD, we examined discs in Bgn-deficient mice. Methods A total of 30 spine specimens were harvested from wild-type (WT) and Bgn-deficient mice. Five specimens for each genotype at 4, 6, and 9 months old were examined in the experiments. Morphometrical and histological analysis of the IVD were performed. Histological gradings were performed separately on nucleus pulposus (NP), annulus fibrosus (AF), and end plate (EP) according to the classification system proposed by Boos et al. Results The Bgn-deficient mice exhibited progressive decreases of NP area with age, which were representative changes consistent with disc degeneration. We found that Bgn-deficient mice developed an early onset of disc degeneration compared to WT mice. The degenerative scores of Bgn-deficient mice were significantly higher than those of WT mice at 4 and 9-month-old. High scores for NP and AF in Bgn-deficient mice significantly affected the difference in total degenerative scores at 9 months of age. Conclusion Bgn deficiency significantly accelerated disc degeneration.

Coupling of small leucine-rich proteoglycans to hypoxic survival of a progenitor cell-like subpopulation in Rhesus Macaque intervertebral disc

“…Our results also suggest that under low oxygen tension, the survival of these cells, termed disc progenitor cells (DPCs), depend on SLRP, which have been previously demonstrated to be essential extracellular matrix components in IVD and are associated to IVD degeneration [16]. Altogether, this study provides support to the existence of progenitor cells native to and normally quiescent in IVD, and a function of proteoglycans as a niche component in promoting their survival under the intrinsic microenvironmental stress.…”

“…IVD composes largely of collagen and proteoglycan in particular collagen I and II, and small leucine-rich proteoglycans (SLRPs) decorin and biglycan [16]. We tested the growth of DPCs cultured on these ECM substrates for 7 days under hypoxia.…”

“…Interestingly, the level of biglycan and decorin expression showed a unique pattern with age and IVD degeneration, in which their expression decreased progressively with age and with severity of degeneration [15]. Notably, biglycanknockout mice developed an early episode of disc degeneration [16]. Thus, it is worth to investigate whether biglycan or decorin is responsible for the IVD tissue-specific progenitor cell-supportive activities.…”

Decorin expression is important for age-related changes in tendon structure and mechanical properties

“…In equine superficial digital flexor tendons and in mice tibialis anterior tendons, aging was shown to increase the modulus (Gillis et al, 1995; Wood et al, 2011). Although biglycan absence has been linked to accelerated decline of intervertebral disks (Furukawa et al, 2009), little is known about SLRPs’ influence on the aging process in tendon.…”

Animal models for studying the etiology and treatment of low back pain

“…61,62 Studies evaluating pain behavior in these models have been limited. Future investigations studying changes in pain behavior in genetic models such as these would be interesting.…”