AGE-DEPENDENT EXPRESSION OF TRANSFORMING GROWTH FACTOR β1 (TGF-β1) AND ITS RECEPTORS, AND AGE-RELATED STIMULATORY EFFECT OF TGF-β1 ON PROTEOGLYCAN SYNTHESIS IN RAT INTERVERTEBRAL DISCS

Age-related alterations of gene expression of transforming growth factor β1 (TGF-β1) and its receptors ( T β Rs ) in tissues derived from rat intervertebral discs were assessed together with TGF-β1-dependent proteoglycan synthesis by the cultured disc cells. Disc tissues and cells were individually harvested from two sites of the coccygeal vertebrae, namely the nucleus pulposus (NP) and annulus fibrosus (AF), which are major distinct components of the intervertebral discs. Semi-quantitative RT-PCR analysis indicated that the level of gene expression of TGF-β1/TGF-β1 receptor type I (TβR-I) of NP decreased with age. In AF, the level of TGF-β1/ T β Rs gene expression did not apparently differ with age. Consistent with the RT-PCR results, stimulation of proteoglycan synthesis by TGF-β1 in NP cells decreased with age. Proteoglycan synthesis by AF cells was also stimulated by TGF-β1. However, levels of this stimulation by AF cells were identical. The present findings indicate that the genetic expression of TGF-β1/ T β R -I and TGF-β1-dependent proteoglycan synthesis decreased with age in NP cells, and further suggest that a loss of proteoglycan synthesis with age in the intervertebral disc is at least in part due to the transcriptional down regulation of TGF-β1/ T βR-I and decreased synthetic ability of proteoglycans in response to TGF-β1 by NP cells.