Expression of proinflammatory cytokines and proinsulin by bone marrow-derived cells for fracture healing in long-term diabetic mice.

BACKGROUND: Diabetes mellitus (DM) causes bone dysfunction due to poor bone quality, leading to severe deterioration in patient of quality of life. The mechanisms of bone metabolism in DM remain unclear, although chemical and/or mechanical factors are known to disrupt the homeostasis of osteoblasts and osteoclasts. The purpose of this study was to identify the changes of osteoblasts and osteoclasts under long-term hyperglycaemic conditions, using a mouse fracture model of long-term hyperglycemia (LT-HG). METHODS: C57BL/6J mice and green fluorescent protein (GFP) -positive bone marrow transplanted C57BL/6J mice with LT-HG, maintained under a state of hyperglycaemia for 2 months, were used in this study. After the experimental fracture, we examined the immunohistochemical expression of proinsulin and tumor necrosis factor (TNF) -α at the fracture site. C57BL/6J fracture model mice without hyperglycaemia were used as controls. RESULTS: In the LT-HG mice, chondrocyte resorption was delayed, and osteoblasts showed an irregular arrangement at the callus site. The osteoclasts were scattered with a decrement in the number of nuclei. The expression of proinsulin was confirmed in bone marrow derived cells (BMDCs) with neovascularization 2 and 3 weeks after fracture. Immunopositivity for TNF-α was also confirmed in immature chondrocytes and BMDCs with neovascularization at 2 weeks, and the number of positive cells was not decreased at 3 weeks. Examination of GFP-grafted hyperglycaemic mice showed that the majority of cells at the fracture site were GFP-positive. Immunohistochemistry showed that the rate of double positives was 15% for GFP and proinsulin and 47% for GFP and TNF-α. CONCLUSION: LT-HG induces an increase in the number of proinsulin and TNF-α positive cells derived from BMDCs. We suggest that proinsulin and TNF-α positive cells are involved in both bone formation and bone resorption after fracture under hyperglycaemic conditions, resulting in the delay of bone healing.

Increased Cellular Expression of Interleukin-6 in Patients With Ossification of the Posterior Longitudinal Ligament.

STUDY DESIGN: We performed histologic, immunohistochemical, immunoblot examination and suspension array analyses of cytokine expression in cultured cells derived from human cervical ossification of the posterior longitudinal ligament (OPLL). OBJECTIVE: To determine the roles of interleukin-6 (IL-6) during the maturation of osteoblasts and chondrocytes associated with the development of OPLL. SUMMARY OF BACKGROUND DATA: Ectopic OPLL affects ~3% of the general population, with a higher incidence in Asian ethnic groups. Alterations in cytokine profiles may influence osteoblast differentiation, but the mechanisms and signaling pathways associated with the ossification process remain unclear. METHODS: Samples were collected from 14 patients with OPLL who had undergone spinal surgery and seven with cervical spondylotic myelopathy without OPLL. Tissue sections were used for histologic and immunohistochemical studies, and primary cells from ligamentum samples were used for cytokine array and immunoblotting. A suspension array was used to measure the concentrations of 27 inflammatory cytokines or growth factors. RESULTS: Suspension array and immunoblot analyses revealed significantly elevated levels of IL-6 in OPLL patients. Alterations in IL-6 concentrations were found to alter the expression of the genes Sox9 , Runx2 , and SIRT1 . In addition, immunohistochemical analysis revealed that these factors are present in mesenchymal cells within the degenerative portion of the ligament matrix that is adjacent to the ossification front. CONCLUSIONS: IL-6 plays a profound role in the osteoblast differentiation process along with the induction of chondrocyte hypertrophy and cell apoptosis in the early stages of ossification in OPLL. These changes in cytokine profiles are essential factors for regulation of the ectopic ossified plaque in OPLL.

Phenotypic classification of knee osteoarthritis according to pain mechanisms; a clinical observational study.

BACKGROUND: Pain in knee osteoarthritis is considered to be nociceptive. Recently, involvement of neuropathic pain and psychosocial factors in knee osteoarthritis has been reported. However, the following details are unclear: 1) How often are neuropathic pain and psychosocial factors involved? And 2) Which patients are associated with neuropathic pain and psychosocial factors? METHODS: In 104 patients with knee osteoarthritis, we evaluated neuropathic pain factor with a painDETECT questionnaire and catastrophic thinking using the pain catastrophizing scale. Pain intensity was assessed using the visual analog scale; patients with scores below the median were defined as low-pain group and others as high-pain group. Radiographic severity was categorized according to the Kellgren-Lawrence classification, with grades I-II and III-IV defined as low- and high-grades, respectively. We compared the painDETECT and pain catastrophizing scale scores between the low- and high-pain groups and low- and high-grade groups. Furthermore, the painDETECT and pain catastrophizing scale scores were compared among the following four groups: low-grade/low-pain, low-grade/high-pain, high-grade/low-pain, and high-grade/high-pain. RESULTS: Neuropathic pain factor and catastrophic thinking were found in 16% and 34% of patients, respectively. There were no significant differences in both painDETECT and pain catastrophizing scale scores between the two pain intensity groups. Between the two groups of radiographic severity, there was no significant difference in the painDETECT scores; however, the pain catastrophizing scale score was significantly high in the low-grade group. In addition, there was no significant difference in the painDETECT scores among the four groups; however, the pain catastrophizing scale scores were significantly higher in low-grade/high-pain than in high-grade/low-pain patients. CONCLUSIONS: Therefore, 64% had only nociceptive pain factor. Catastrophic thinking was strong in patients with low radiographic severity, especially in those with high pain intensity. Patients with neuropathic pain factor could not be identified from radiographic severity and pain intensity.

Cytokine Profile From the Ligamentum Flavum in Patients with Ossification of the Posterior Longitudinal Ligament in the Cervical Spine.

STUDY DESIGN: Histological, immunohistochemical, and suspension array analyses of cytokine expression in human cervical ossification of the posterior longitudinal ligament (OPLL). OBJECTIVES: The aim of this study was to determine whether changes in the cytokine profile reflect the maturation of chondrocytes and osteoblasts are associated with OPLL development. SUMMARY OF BACKGROUND DATA: OPLL progresses gradually over a prolonged period and may lead to serious spinal cord complications. However, treatment methods only include conservative therapy for neurological symptoms or surgical decompression, whereas preventive therapy for OPLL remains nonexistent. METHODS: Ligamentous samples were harvested from 24 patients with OPLL who underwent spinal surgery, and five control samples from cervical spondylotic myelo/radiculopathy patients without OPLL. Tissue sections were used for immunohistochemical studies and primary cells were cultured from the ligamentous samples for cytokine profiling. Using a suspension array system, concentrations of 27 inflammatory cytokines or growth factors were measured to generate the cytokine profiles. RESULTS: Suspension array and immunoblot analysis revealed significant increments in the levels of interleukin (IL)-6, IL-1α, basic fibroblast growth factor, and RANTES in patients with OPLL. Immunohistochemical analysis further revealed that these factors were present in mesenchymal cells within the degenerative portion of the ligamentous matrix. CONCLUSION: Our findings suggest that specific changes in the cytokine profile during ossification promote osteoblast differentiation, thereby providing new insights into OPLL pathogenesis. Moreover, this work supports the development of a new therapeutic method for preventing OPLL progression by regulating the cytokine profiles.Level of Evidence: 3.

Knee osteoarthritis with patellar dislocation treated by total knee arthroplasty using a lateral parapatellar approach-ingenuity of exposure and closure.

Knee osteoarthritis with patellar dislocation is a rare and difficult-to-treat condition. Several reports of total knee arthroplasty (TKA) combined with various realignment procedures have been published. A 77-year-old man with knee pain was referred to our hospital. Plain radiography revealed a laterally dislocated patella, with osteoarthritic changes in the femorotibial joint. He simply underwent TKA via a lateral parapatellar approach without realignment. We devised methods of exposure and closure to maximize the effect of lateral release by the lateral parapatellar approach. TKA using the lateral parapatellar approach might be effective in treating knee osteoarthritis with patellar dislocation.

Total knee arthroplasty for treatment of osteoarthritis with prolonged patellar dislocation.

Prolonged dislocation of the patella is a rare condition and is often related to severe osteoarthritis (OA) of the femorotibial (FT) joint. For this condition's treatment, numerous surgical techniques using total knee arthroplasty (TKA) have been published. To the best of our knowledge, this case report is the first description of the use of lateral release alone to treat recurrent patellar subluxation with TKA. An interesting point in this case is that the patient had a good recovery after TKA in spite of quite a long-term (a duration of almost 55 years) dislocation of her patella and development of secondary OA. We describe a case that we treated by TKA for FT-OA with a prolonged patellar dislocation. We were able to obtain good patellar reduction without additional surgery by performing adequate lateral release of the patellar retinaculum. This clinical case indicates the usefulness of lateral patellar retinaculum release for obtaining stable patellar tracking in TKA for FT-OA with remaining lateral patellar dislocation. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).