Asporin and transforming growth factor-beta gene expression in osteoblasts from subchondral bone and osteophytes in osteoarthritis

J Orthop Sci. 2009 Nov;14(6):738-47. doi: 10.1007/s00776-009-1401-4. Epub 2009 Dec 8.

Abstract

Background: To clarify the significance of subchondral bone and osteophytes in the pathology of osteoarthritis (OA), we investigated the expression of asporin (ASPN), transforming growth factor-beta1 (TGF-beta1), TGF-beta2, TGF-beta3, and runt-related transcription factor-2 (Runx2) genes involved in bone metabolism.

Methods: Osteoblasts were isolated from 19 patients diagnosed with knee OA and from 4 patients diagnosed with femoral neck fracture. Osteoblast expression of mRNA encoding ASPN, TGF-beta1, TGF-beta2, TGF-beta3, and Runx2 was analyzed using real-time RT-PCR.

Results: Expression of ASPN, TGF-beta1, and TGF-beta3 mRNA in the subchondral bone and osteophytes of OA patients increased compared with that of non-OA patients. The ratio of ASPN to TGF-beta1 mRNA in patients with severe cartilage damage was higher than that in patients with mild cartilage damage.

Conclusions: The increased ratio of ASPN mRNA to TGF-beta1 mRNA in patients with severe relative to mild cartilage damage indicates that increased ASPN mRNA expression was significantly associated with the severity of cartilage degeneration. This finding suggests that ASPN may regulate TGF-beta1-mediated factors in the development of OA, which may provide clues as to the underlying pathology of OA.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Case-Control Studies
  • Cells, Cultured
  • Extracellular Matrix Proteins / genetics*
  • Extracellular Matrix Proteins / metabolism
  • Female
  • Furans
  • Gene Expression Profiling
  • Humans
  • Male
  • Osteoarthritis, Knee / genetics*
  • Osteoarthritis, Knee / metabolism
  • Osteoblasts / metabolism*
  • Osteophyte / genetics*
  • Osteophyte / metabolism
  • RNA, Messenger / metabolism*
  • Severity of Illness Index
  • Thiophenes
  • Transforming Growth Factor beta1 / genetics*
  • Transforming Growth Factor beta1 / metabolism
  • Transforming Growth Factor beta2 / genetics
  • Transforming Growth Factor beta2 / metabolism
  • Transforming Growth Factor beta3 / genetics
  • Transforming Growth Factor beta3 / metabolism

Substances

  • 3,4-bis-(2,4,5-trimethyl-thiophen-3-yl)furan-2,5-dione
  • ASPN protein, human
  • Extracellular Matrix Proteins
  • Furans
  • RNA, Messenger
  • Thiophenes
  • Transforming Growth Factor beta1
  • Transforming Growth Factor beta2
  • Transforming Growth Factor beta3