PTH[1-34] improves the effects of core decompression in early-stage steroid-associated osteonecrosis model by enhancing bone repair and revascularization

Abstract

Steroid-associated osteonecrosis (SAON) might induce bone collapse and subsequently lead to joint arthroplasty. Core decompression (CD) is regarded as an effective therapy for early-stage SAON, but the prognosis is unsatisfactory due to incomplete bone repair. Parathyroid hormone[1–34] (PTH[1–34]) has demonstrated positive efficacy in promoting bone formation. We therefore evaluated the effects of PTH on improving the effects of CD in Early-Stage SAON. Distal femoral CD was performed two weeks after osteonecrosis induction or vehicle injection, with ten of the ON-induced rabbits being subjected to six-week PTH[1–34] treatment and the others, including ON-induced and non-induced rabbits, being treated with vehicle. MRI confirmed that intermittent PTH administration improved SAON after CD therapy. Micro-CT showed increased bone formation within the tunnel. Bone repair was enhanced with decreased empty osteocyte lacunae and necrosis foci area, resulting in enhanced peak load and stiffness of the tunnel. Additionally, PTH enlarged the mean diameter of vessels in the marrow and increased the number of vessels within the tunnels, as well as elevated the expression of BMP-2, RUNX2, IGF-1, bFGF and VEGF, together with serum OCN and VEGF levels. Therefore, PTH[1–34] enhances the efficacy of CD on osteogenesis and neovascularization, thus promoting bone and blood vessels repair in the SAON model.

Bone Vasculature and Bone Marrow Vascular Niches in Health and Disease

“…EC-specific deletion of VEGFR2 results in reduction and disorganization of blood vessels in the metaphyseal region closed to the growth plate. (75) VEGFA exists in multiple isoforms-VEGF 120 , VEGF 164 , and VEGF 188 in mouse and VEGF 121 , VEGF 145 , VEGF 165 , VEGF 183 , VEGF 186 , VEGF 189 , and VEGF 206 in human, which elicit diverse biological processes. (76,77) Nevertheless, reduced endochondral angiogenesis and mineralization occurs in mice expressing only VEGF 120 isoform.…”

Prevalence of glucocorticoid induced osteonecrosis in the mouse is not affected by treatments that maintain bone vascularity

“…Human PTH (1–34) counteracts the adverse effects of GCs on osteoblast and osteocyte viability, bone formation, and bone strength ( Weinstein et al, 2010 ; Yao et al, 2008b ). Human PTH (1–34) also improves the effects of core decompression in an ONFH animal model, partially through revascularization ( Zhou et al, 2017 ).…”

Cepharanthine Prevents Estrogen Deficiency-Induced Bone Loss by Inhibiting Bone Resorption

“…All the left femurs from mice were decalcified and embedded into paraffin as previously described (Zhou et al, 2017 ). Specimens were cut into 5 μm-thick sections along the coronal plane from anterior to posterior.…”

“…The blood was collected and centrifuged at 2,000 rpm for 20 min to isolate serum as previously described (Zhou et al, 2017 ). Subsequently, serum concentrations of CTX-1 and P1NP were measured according to the ELISA kit manufacturer's protocol.…”

“…The extraction of total RNA was performed using an RNAeasy Mini Kit (Qiagen, Valencia, CA, USA) according to the manufacturer's instructions. cDNA was synthesized and qPCR was performed as described previously (Zhou et al, 2017 ). GAPDH was utilized as the housekeeping gene and all experiments were repeated independently at least three times.…”