Local Injection of Growth Hormone for Temporomandibular Joint Osteoarthritis

Abstract

Purpose: Osteoarthritis (OA) of the temporomandibular joint (TMJ) elicits cartilage and subchondral bone defects. Growth hormone (GH) promotes chondrocyte growth. The aim of this study was to evaluate the efficacy of intra-articular injections of GH to treat TMJ-OA.

Materials and methods: Monosodium iodoacetate (MIA) was used to induce OA in the TMJs of rats. After confirming the induction of OA, recombinant human GH was injected into the articular cavities of rats. Concentrations of GH and IGF-1 were measured in the blood and synovial fluid, and OA grades of cartilage and subchondral bone degradation were recorded by histological examination and micro-computed tomography.

Results: MIA-induced OA in the rat TMJ upregulated insulin-like growth factor-1 (IGF-1) rather than GH levels. GH and IGF-1 concentrations were increased after local injection of GH, compared with controls. Locally injected GH lowered osteoarthritic scores in the cartilage and subchondral bone of the TMJ.

Conclusion: Intra-articular injection of GH improved OA scores in rat TMJs in both cartilage and subchondral bone of the condyles without affecting condylar bone growth. These results suggest that intra-articular injection of human GH could be a suitable treatment option for TMJ-OA patients in the future.

Keywords: Growth hormone; intraarticular injection; osteoarthritis; temporomandibular joint.

Fig. 1. Diagram of the study design. OA, osteoarthritis; GH, growth hormone; PBS, phosphate buffered saline; CT, micro-computed tomography.

Fig. 2. OA scoring of the bone (micro-CT) and cartilage (histologic finding). (A-D) Central sagittal micro-CT images of erosive condyles to score subchondral bone: bony OA score=0 (A , None), 1 (B, Minor), 2 (C, Moderate), and 3 (D, Severe). (E-J) Histologic findings (Masson's trichrome staining): healthy (E), cartilaginous OA score=1 (F), 2 (G), 3 (H), 4 (I), and 5 (J). The black scale bar in the histological images represents 300 µm. OA, osteoarthritis; CT, computed tomography.

Fig. 3. GH injections into the TMJ increase serum GH levels, but not IGF-1 levels. After two and four injections of PBS(Rt) or GH(Lt) into the TMJ, GH (A) and IGF-1 (B) concentrations in serum were measured using ELISA . Healthy (n=2), OA-induced only (n=5, allowed to self-heal after induction of OA), and OA+GH injected (n=10). ^*p=0.003 (Mann-Whitney test). GH, growth hormone; IGF-1, insulin-like growth factor 1; PBS, phosphate buffered saline; TMJ, temporomandibular joint; ELISA, enzyme-linked immunosorbent assay; OA, osteoarthritis.

Fig. 4. GH injections into the TMJ increase IGF-1 levels in synovial fluid. After two and four injections of PBS(Rt) or GH(Lt) into the TMJ, the GH (A) and IGF-1 (B) concentrations in synovial fluid from the TMJ were measured by ELISA. OA-induced only (n=5, allowed to self-heal after induction of OA), OA+PBS injected (n=10), and OA+GH injected (n=10). ^*p=0.016 (Kruskal-Wallis test). GH, growth hormone; TMJ, temporomandibular joint; IGF-1, insulin-like growth factor 1; PBS, phosphate buffered saline; ELISA, enzyme-linked immunosorbent assay; OA, osteoarthritis.

Fig. 5. Local injection of GH ameliorates OA joint in subchondral bone of the temporomandibular. OA scores were determined using in vivo micro-CT images performed before PBS or GH administration and after two (A) and four (B) injections of PBS or GH. OA-induced only (n=5, allowed to self-heal after induction of OA), OA+PBS injected (n=10), and OA+GH injected (n=10). ^*Differences were statistically significant at p<0.05, ^†Differences were statistically significant at p<0.01. OA, osteoarthritis; CT, computed tomography; CT1, OA score observed on initial CT images immediately after OA was induced; CT2, OA score observed on CT images after two injections; CT3, OA score observed on CT images after four injections; GH, growth hormone; TMJ-OA, osteoarthritis of the temporomandibular joint; micro-CT, micro-computed tomography; PBS, phosphate buffered saline.

Fig. 6. GH injection into the MIA-induced OA of the TMJ area significantly improves OA scores in the cartilage. (A) All images were obtained from one rat after four injections of GH in the left TMJ (a, b, c) and PBS in the right TMJ (d, e, f). TMJ-OA was induced by MIA injection, and micro-CT images (CT1) were acquired at 2 weeks after MIA injection to confirm OA induction (a, d). Treatment with GH (b) or PBS (e) injection was administered four times, and images (CT3) were taken after administration. Histologic findings of panels (b) and (e) were observed using Masson's trichrome stain respective to (c) and (f). The black scale bar in the histological images represents 500 µm. (B) Histologic OA scores were compared between PBS- and GH-injected groups. OA-induced only (n=5, allowed to self-heal after induction of OA), OA+PBS injected (n=10), and OA+GH injected (n=10). ^*p=0.004 (Mann-Whitney test). OA, osteoarthritis; GH, growth hormone; MIA, monosodium iodoacetate; TMJ-OA, osteoarthritis of the temporomandibular joint; micro-CT, micro-computed tomography; PBS, phosphate buffered saline.