Parathyroid hormone (1-34) prevents cartilage degradation and preserves subchondral bone micro-architecture in guinea pigs with spontaneous osteoarthritis

Objective: To assess whether parathyroid hormone (PTH) (1-34) could improve the micro-structure of subchondral bone, and retard cartilage degradation in a naturally occurring Osteoarthritis (OA) model. Design: Forty-eight 1-month-old guinea pigs were divided into two groups: 32 were treated by normal saline (NS) and sacrificed at 1, 3, 6 and 9 months of age; the other 16 received PTH (1-34) from 3 months, and were sacrificed at 6 and 9 months. Masson staining and the Osteoarthritis Research Society International (OARSI) grade scores were used to assess cartilage degradation. Immunohistochemistry analyses of type-II collagen, matrix metalloproteinases-13 (MMP-13) and sclerostin (SOST) in the cartilage, osteoprotegerin (OPG) and receptor activator of nuclear factor-kB ligand (RANKL) and PTH receptor (PTH1R) in the cartilage and subchondral bone were performed. Subchondral bone micro-architecture was assessed by micro-computed tomography (micro-CT). Results: Histological analyses revealed OA occurred at 3 months of age and was more severe with increasing age, and PTH (1-34) reduced the OARSI scores at 6 and 9 months of age. Micro-CT analysis indicated that PTH (1-34) treatment increased the bone volume ratio and bone mineral density (BMD), while retarding the subchondral trabecular bone micro-architectural changes from rod-like to plate-like. Immunohistochemical staining demonstrated that PTH (1-34) treatment increased type-II collagen expression and decreased SOST and MMP-13 expression in the cartilage, while elevating the PTH1R, OPG/RANKL expression ratio in the cartilage and subchondral trabecular bone when compared with the control groups. Conclusions: PTH (1-34) can prevent cartilage damage progression and retard the deterioration of subchondral trabecular bone in guinea pigs. (C) 2014 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.