Bone sialoprotein as a potential key factor implicated in the pathophysiology of osteoarthritis

Osteoarthritis Cartilage. 2014 Apr;22(4):547-56. doi: 10.1016/j.joca.2014.01.010. Epub 2014 Feb 13.


Objective: We previously identified an association between bone sialoprotein (BSP) and osteoarthritic (OA) chondrocyte hypertrophy but the precise role of BSP in ostearthritis (OA) has not been extensively studied. This study aimed to confirm the association between BSP and OA chondrocyte hypertrophy, to define its effect on molecules produced by chondrocytes and to analyse its association with cartilage degradation and vascular density at the osteochondral junction.

Method: Human OA chondrocytes were cultivated in order to increase hypertrophic differentiation. The effect of parathyroid hormone-related peptide (PTHrP), interleukin (IL)-1β or tumour necrosis factor (TNF)-α on BSP was analysed by real-time reverse transcription polymerase chain reaction (RT-PCR) and western blot. The effects of BSP on OA chondrocytes production of inflammatory response mediators (IL-6, nitric oxide), major matrix molecule (aggrecan), matrix metalloprotease-3 and angiogenic factors (vascular endothelial growth factor, basic fibroblast growth factor, IL-8, and thrombospondin-1) were investigated. BSP was detected by immunohistochemistry and was associated with cartilage lesions severity and vascular density.

Results: PTHrP significantly decreased BSP, confirming its association with chondrocyte hypertrophy. In presence of IL-1β, BSP stimulated IL-8 synthesis, a pro-angiogenic cytokine but decreased the production of TSP-1, an angiogenesis inhibitor. The presence of BSP-immunoreactive chondrocytes in cartilage was associated with the severity of histological cartilage lesions and with vascular density at the osteochondral junction.

Conclusion: This study supports the implication of BSP in the pathology of OA and suggests that it could be a key mediator of the hypertrophic chondrocytes-induced angiogenesis. To control chondrocyte hypertrophic differentiation is promising in the treatment of OA.

Keywords: Angiogenesis; Bone sialoprotein; Chondrocyte hypertrophy; Osteoarthritis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aggrecans / metabolism
  • Blotting, Western
  • Chondrocytes / metabolism
  • Chondrocytes / pathology*
  • Fibroblast Growth Factor 2 / metabolism
  • Humans
  • In Vitro Techniques
  • Integrin-Binding Sialoprotein / metabolism*
  • Interleukin-1beta / pharmacology
  • Interleukin-6 / metabolism
  • Interleukin-8 / metabolism
  • Matrix Metalloproteinase 3 / metabolism
  • Nitric Oxide / metabolism
  • Osteoarthritis, Knee / metabolism
  • Osteoarthritis, Knee / pathology*
  • Parathyroid Hormone-Related Protein / pharmacology
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Thrombospondin 1 / metabolism
  • Tumor Necrosis Factor-alpha / pharmacology
  • Vascular Endothelial Growth Factors / metabolism


  • Aggrecans
  • Integrin-Binding Sialoprotein
  • Interleukin-1beta
  • Interleukin-6
  • Interleukin-8
  • Parathyroid Hormone-Related Protein
  • Thrombospondin 1
  • Tumor Necrosis Factor-alpha
  • Vascular Endothelial Growth Factors
  • Fibroblast Growth Factor 2
  • Nitric Oxide
  • Matrix Metalloproteinase 3