Oestrogen and parathyroid hormone alleviate lumbar intervertebral disc degeneration in ovariectomized rats and enhance Wnt/β-catenin pathway activity

Abstract

To investigate the mitigation effect and mechanism of oestrogen and PTH on disc degeneration in rats after ovariectomy, as well as on Wnt/β-catenin pathway activity, thirty 3-month-old rats were ovariectomized and divided into three groups. Ten additional rats were used as controls. Eight weeks later, the rats were administered oestrogen or PTH for 12 weeks, and then discs were collected for tests. Results showed that nucleus pulposus cells in the Sham group were mostly notochord cells, while in the OVX group, cells gradually developed into chondrocyte-like cells. Oestrogen or PTH could partly recover the notochord cell number. After ovariectomy, the endplate roughened and endplate porosity decreased. After oestrogen or PTH treatment, the smoothness and porosity of endplate recovered. Compared with the Sham group, Aggrecan, Col2a and Wnt/β-catenin pathway expression in OVX group decreased, and either oestrogen or PTH treatment improved their expression. The biomechanical properties of intervertebral disc significantly changed after ovariectomy, and oestrogen or PTH treatment partly recovered them. Disc degeneration occurred with low oestrogen, and the underlying mechanisms involve nutrition supply disorders, cell type changes and decreased Wnt/β-catenin pathway activity. Oestrogen and PTH can retard disc degeneration in OVX rats and enhance Wnt/β-catenin pathway activity in nucleus pulposus.

Ciliary parathyroid hormone signaling activates transforming growth factor-β to maintain intervertebral disc homeostasis during aging

“… 46 iPTH injection improves the adjacent segment disc degeneration by enhancing lumber fusion 47 and alleviates disc degeneration in ovariectomized osteoporotic mice by up-regulation of Wnt/β-catenin pathway. 48 In this study, we demonstrate that PTH1R is expressed in the NP cells of notochordal origin to maintain disc homeostasis particularly during aging by directly activating TGF-β signaling in NP cells in addition to its expression in vertebral bodies and endplates. The results suggested that expression of PTH1R in disc cells promotes the mobility of amphibians in their adaptation to terrestrial life from aquatic vertebrates.…”

“…During aging or disc degeneration, endplates become calcified and sclerotic, leading to less efficient diffusion of nutrients in support for discs. 56 , 57 iPTH will stimulate osteoclast resorption of the sclerotic endplates and induce native bone formation through remodeling, 48 and the process likely improves their diffusion property for the disc. Similarly, iPTH stimulates bone remodeling and improves bone quality for the vertebral bodies.…”

Parathyroid hormone 1‑34 inhibits senescence in rat nucleus pulposus cells by activating autophagy via the m‑TOR pathway

“…For example, Luo et al ( 6 ) identified a close relationship between IDD and osteoporosis in ovariectomized rats, and speculated that the mechanism involved was related to the integrity and function of adjacent structures of intervertebral discs in the spine. Adjacent segment disc degeneration is very common in women with osteoporosis, thus indicating that osteoporosis might represent one of the causative agents of IDD ( 7 ). Research has shown that the endplate of patients with osteoporosis is under high pressure and that this can cause endplate calcification.…”

“…PTH is also known to regulate the synthesis and metabolism of intervertebral disc cells and inhibit potential calcification molecules via the mitogen-activated protein kinase (MAPK) and protein kinase A (PKA) signaling pathways ( 9 ). It has also been reported that PTH cannot only promote anabolic metabolism, but can also inhibit degradation of the extracellular matrix within intervertebral discs ( 7 ). Indeed, animal experiments have established that PTH can relieve disc degeneration in rat models of osteoporosis ( 7 ).…”

Confirmation and preliminary analysis of circRNAs potentially involved in human intervertebral disc degeneration

“…Several signaling pathways have been reported to be involved in IDD, including the Wnt/β-catenin, the P53/P21, the interleukin, and the tumor growth factor-β pathways (26,(29)(30)(31)(32)(33). These signaling pathways have important roles in regulating IDD.…”