Altered Expression of the Hedgehog Pathway Proteins BMP2, BMP4, SHH, and IHH Involved in Knee Cartilage Damage of Patients With Osteoarthritis and Kashin-Beck Disease

Cartilage. 2022 Jan-Mar;13(1):19476035221087706. doi: 10.1177/19476035221087706.

Abstract

Objective: To investigate the expression of Hedgehog (HH) signaling pathway proteins in knee articular cartilage from Kashin-Beck disease (KBD) and osteoarthritis (OA) patients.

Methods: Knee articular cartilage samples were collected from normal (N), OA, and KBD adults (aged 38-60 years) and divided into 3 groups with 6 subjects in each group. The localization of the HH pathway proteins bone morphogenetic protein 2 (BMP2), bone morphogenetic protein 4 (BMP4), Sonic hedgehog (SHH), and Indian hedgehog (IHH) was observed with the microscope after immunohistochemical (IHC) staining. Positive staining cell rates of each proteins were compared.

Results: The strongest stainings of all proteins were observed in the middle zones of all 3 groups. The positive staining rates of BMP4 and IHH were significantly lower in the OA and KBD groups than those in the N group in all 3 zones. The positive staining rates of BMP2 and SHH tend to be lower in the OA and KBD groups than those in the N group in the deep zone, while higher in the OA and KBD groups than those in the N group in superficial and middle zones.

Conclusions: Altered expression of the HH pathway proteins BMP2, BMP4, SHH, and IHH was found in OA and KBD articular cartilage. There seemed to be a compensatory effect between SHH and IHH in cartilage damage. Further studies on the pathogenesis of OA and KBD may be carried out from these aspects in the future.

Keywords: Hedgehog pathway; Kashin-Beck disease; articular cartilage; immunohistochemistry; osteoarthritis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Protein 4 / metabolism
  • Cartilage, Articular* / pathology
  • Chondrocytes / metabolism
  • Hedgehog Proteins / metabolism
  • Humans
  • Kashin-Beck Disease*
  • Osteoarthritis* / metabolism

Substances

  • BMP2 protein, human
  • BMP4 protein, human
  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Protein 4
  • Hedgehog Proteins
  • SHH protein, human