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.

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For the total synthesis of (+)-taxusin, the AC-ring fragment 8 was prepared from an optically active 2-bromo-3-siloxycyclohexenecarbacetal 5 via 4 steps and was converted to the dienol silyl ether 13. The thus-obtained 13 underwent B-ring cyclization in the presence of Me2AlOTf to produce the ABC endo-tricarbocycle 14 having C9α, C10β-substituents, which was converted to the cyclopropyl ketone 21a. Introduction of C19 methyl via reductive cleavage of the cyclopropane ring under Birch conditions and successive in situ treatment of the resulting enol with methanol gave the C3α-protonated ketone 24. Next, 24 was converted to the allylsilane 29, which was then oxidized with m-CPBA to produce the fully functionalized taxusin carbon skeleton. Finally, removal of the silyl protecting groups followed by acetylation completed the total synthesis of (+)-taxusin.