Expression of parathyroid hormone‐related peptide in human osteoarthritis

Abstract

To evaluate the involvement of the expression of parathyroid hormone-related peptide gene in human articular cartilage pathology, we performed immunohistochemical staining and in situ hybridization on specimens of femoral head cartilage obtained from 15 patients with osteoarthritis, 11 with rheumatoid arthritis, and 12 control subjects. Parathyroid hormone-related peptide-positive chondrocytes were observed predominantly in degenerated lesions of osteoarthritic tissue and were less evident in rheumatoid arthritic samples, while the normal cartilage expressed little parathyroid hormone-related peptide. In addition, the level of parathyroid hormone-related peptide expression was clearly dependent on the degree of cartilage degeneration; cartilage tissues with moderate degenerative changes contained more positive chondrocytes compared with mildly or severely degenerated cartilage. In situ hybridization confirmed the localization of parathyroid hormone-related peptide protein and demonstrated intense expression of mRNA of the peptide in osteoarthritic samples. This is the first demonstration of parathyroid hormone-related peptide expression in chondrocytes from pathologic articular cartilage of humans. Our results suggest that parathyroid hormone-related peptide may be involved in the pathophysiology of osteoarthritis.

Parathyroid hormone‐related peptide and Indian hedgehog expression patterns in naturally acquired equine osteochondrosis

“…However, there is evidence that PTH-rP plays a role in the development of articular cartilage, as its expression has been shown in rat articular cartilage during the pre-and postnatal period [31] and in juvenile chickens [20]. In addition, PTHrP and PTH-rP receptor expression have been found in normal human articular cartilage, with increased levels expressed in osteoarthritis [22,30].…”

Production of parathyroid hormone‐related peptide by synovial fibroblasts in human osteoarthritis

“…The accumulation of PTHrP in synovial fluid has been reported by Kohno et al [7] and Okano et al [8]. The synovial fluid level of the C-terminal region of PTHrP (CPTHrP) was markedly higher in rheumatoid arthritis compared with control and osteoarthritis groups, while no differences in circulatory C-PTHrP in serum were present among the three groups.…”

“…In contrast, the synovial fluid level of the Nterminal region of PTHrP (N-PTHrP), which has a stimulatory effect on bone resorption [17], was marginally higher in osteoarthritis. Moreover, immunoreactivity to PTHrP (38 64, mid-portion) antibody was more frequently identified in osteoarthritic cartilage (specimens) than rheumatoid arthritic specimens and control subjects [8]. PTHrP produced in arthral tissue likely has important roles in osteoarthritis and subsequent cartilage degeneration and bone destruction.…”

“…Recently it has been reported that synovial fluids from patients with osteoarthritis and rheumatoid arthritis contain high levels of PTHrP [7]. Expression of PTHrP in normal and abnormal cartilage tissue from patients with osteoarthritis or rheumatoid arthritis, using immunohistochemistry and in situ hybridization, was also reported [8]. Furthermore, many kinds of cells in arthral tissue, such as osteoclasts and osteoblasts of deteriorating bony tissue, synovial cells in the superficial layer, macrophages in the deeper layer and *Corresponding author.…”

Extracellular nucleotide metabolism and signaling in the pathophysiology of articular cartilage

“…Parathyroid hormone-related proteins (PTHrP) are detected in human OA synovial fluid (130) and articular cartilage (131). Whereas PTHrP are widely expressed in normal tissues, the PTHrP 1-173 isoform is selectively expressed in articular cartilage and is up-regulated 3-5-fold in OA (132).…”