Mechanical unloading induces disuse muscle atrophy and bone loss, but the details in mechanism involved in those pathophysiological conditions are not fully understood. Interaction between muscle and bone has been recently noted. Here, we investigated the roles of humoral factors linking muscle to bone during mechanical unloading using mice with hindlimb unloading (HU) and sciatic neurectomy (SNX). HU and SNX reduced muscle volume surrounding the tibia, tissue weights of soleus and gastrocnemius muscle, and trabecular bone mineral density (BMD) in the tibia of mice. Among humoral factors linking muscle to bone, HU and SNX reduced fibronectin type III domain-containing 5 (FNDC5) mRNA levels in the soleus muscle of mice. Simple regression analysis revealed that FNDC5 mRNA levels in the soleus muscle were positively related to trabecular BMD in the tibia of control and HU mice as well as sham and SNX mice. Moreover, FNDC5 mRNA levels were negatively correlated with receptor activator of nuclear factor-κB ligand (RANKL) mRNA levels in the tibia of control and HU mice. Irisin, a product of FNDC5, suppressed osteoclast formation from mouse bone marrow cells and RANKL mRNA levels in primary osteoblasts. FNDC5 mRNA levels elevated by fluid shear stress were antagonized by bone morphogenetic protein (BMP) and phosphatidylinositol 3-kinase (PI3K) signaling inhibitors in myoblastic C2C12 cells. In conclusion, the present study first showed that mechanical unloading reduces irisin expression in the skeletal muscle of mice presumably through BMP and PI3K pathways. Irisin might be involved in muscle/bone relationships regulated by mechanical stress in mice.

BackgroundSubchondral osteopenia is important for the pathophysiology of osteoarthritis (OA). Although previous studies suggest that plasminogen activator inhibitor-1 (PAI-1), an inhibitor of fibrinolysis, is related to bone metabolism, its role in OA remains unknown. We therefore investigated the roles of PAI-1 in the subchondral bone in OA model mice.MethodsWild type (WT) and PAI-1-deficient (KO) mice were ovariectomized (OVX), and then destabilization of the medial meniscus (DMM) surgery was performed.ResultsDMM and OVX significantly decreased the trabecular bone mineral density of the subchondral bone evaluated by quantitative computed tomography in PAI-1 KO mice. The effects of OVX and/or PAI-1 deficiency on the OARSI score for the evaluation of the progression of knee degeneration were not significant. PAI-1 deficiency significantly augmented receptor activator nuclear factor κB ligand mRNA levels enhanced by IL-1β in mouse primary osteoblasts, although it did not affect osteoblast differentiation. Moreover, PAI-1 deficiency significantly increased osteoclast formation from mouse bone marrow cells.ConclusionWe showed that PAI-1 deficiency accelerates the subchondral osteopenia after induction of OA in mice. PAI-1 might suppress an enhancement of bone resorption and subsequent subchondral osteopenia after induction of OA in mice.

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We first demonstrated that PAI-1 is involved in MMP expression enhanced by IL-1β in murine chondrocytes. PAI-1 might be crucial for the cartilage matrix degradation and the impaired chondrogenesis by IL-1β in mice.

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Purpose There is no consensus on intraoperative references for the posterior tibial slope (PTS) in medial unicompartmental knee arthroplasty (UKA). An arthroscopic hook probe placed on the medial second quarter of the medial tibial plateau (MTP) in an anteroposterior direction may be used as a direct anatomical reference for the PTS. The purpose of this study is to investigate availability and accuracy of this method. Methods Marginal osteophyte formation and subchondral depression of the MTP, and angles between the bony MTP and the cartilage MTP were retrospectively evaluated using preoperative sagittal MRI of 73 knees undergoing medial UKA. In another 36 knees, intraoperative lateral knee radiographs with the probe placed on the MTP were prospectively taken in addition to the preoperative MRI. Then, angles between the bony MTP and the probe axis and angles between the preoperative bony MTP and the postoperative implant MTP were measured. Results Among 73 knees, one knee with Grade 4 osteoarthritis had a posterior osteophyte higher than the most prominent point of the cartilage MTP. No subchondral depression affected the direct reference of the MTP. Mean angle between the bony MTP and the cartilage MTP was − 0.8°±0.7° (-2.6°-1.0°, n = 72), excluding the one knee with “high” osteophyte. Mean angle between the bony MTP and the probe axis on the intraoperative radiograph was − 0.6°±0.4° (-1.7-0.0, n = 36). Mean angle between the pre- and the postoperative MTP was − 0.5°±1.5° (-2.9°-1.8°). Root mean square (RMS) error of these two PTS angles was 1.6° with this method. Conclusion Cartilage remnants, osteophyte formation and subchondral bone depression does not affect the direct referencing method in almost all knees for which medial UKA is indicated. When the posterior “high” osteophyte of the MTP is noted on preoperative radiograph, preoperative MRI or CT scan is recommended to confirm no “high” osteophyte on the medial second quarter. Accuracy of this method seems equal to that of the robotic-assisted surgery (the RMS error in previous reports, 1.6°-1.9°).

There has been no consensus about how to determine the individual posterior tibial slope (PTS) intraoperatively. The purpose of this study was to investigate whether the tibial plateau could be used as a reference for reproducing individual PTS during medial unicompartmental knee arthroplasty (UKA). Preoperative computed tomography (CT) data from 48 lower limbs for medial UKA were imported into a three-dimensional planning software. Digitally reconstructed radiographs were created from the CT data as the lateral knee plain radiographs and the radiographic PTS angle was measured. Then, the PTS angles on the medial one-quarter and the center of the MTP (¼ and ½ MTP, respectively), and that on the medial tibial eminence (TE) were measured on the sagittal multiplanar reconstruction image. Finally, 20 lateral knee radiographs with an arthroscopic probe placed on the ¼ and the ½ MTP were obtained intraoperatively, and the angle between the axis of the probe and the tangent line of the plateau was measured. The mean radiographic PTS angle was 7.9 ± 3.0 degrees (range: 1.7–13.6 degrees). The mean PTS angles on the ¼ MTP, the ½ MTP, and the TE were 8.1 ± 3.0 degrees (1.2–13.4 degrees), 9.1 ± 3.0 degrees (1.4–14.7 degrees), and 9.9 ± 3.1 degrees (3.1–15.7 degrees), respectively. The PTS angles on the ¼ MTP and the ½ MTP were strongly correlated with the radiographic PTS angle (r =0.87 and 0.80, respectively, p < 0.001). A statistically significant difference was observed between the mean angle of the radiographic PTS and the PTS on the TE (p < 0.01). The mean angle between the axis of the probe and the tangent line of the tibial plateau was −0.4 ± 0.9 degrees (−2.3–1.3 degrees) on the ¼ MTP and −0.1 ± 0.7 degrees (−1.5–1.2 degrees) on the ½ MTP, respectively. An area from the medial one-quarter to the center of the MTP could be used as an anatomical reference for the individual PTS.

Purpose There is no consensus on intraoperative references for the posterior tibial slope (PTS) in medial unicompartmental knee arthroplasty (UKA). An arthroscopic hook probe placed on the medial second quarter of the medial tibial plateau (MTP) in an anteroposterior direction may be used as a direct anatomical reference for the PTS. The purpose of this study is to investigate the availability and accuracy of this method. Methods Marginal osteophyte formation and subchondral depression of the MTP and angles between the bony MTP and the cartilage MTP were retrospectively evaluated using preoperative sagittal MRI of 73 knees undergoing medial UKA. In another 36 knees, intraoperative lateral knee radiographs with the probe placed on the MTP were prospectively taken in addition to the preoperative MRI. Then, angles between the bony MTP and the probe axis and angles between the preoperative bony MTP and the postoperative implant MTP were measured. Results Among 73 knees, one knee with grade 4 osteoarthritis had a posterior osteophyte higher than the most prominent point of the cartilage MTP. No subchondral depression affected the direct reference of the MTP. The mean angle between the bony MTP and the cartilage MTP was −0.8° ± 0.7° (−2.6°–1.0°, n = 72), excluding one knee with a “high” osteophyte. The mean angle between the bony MTP and the probe axis on the intraoperative radiograph was −0.6° ± 0.4° (−1.7–0.0, n = 36). The mean angle between the pre- and postoperative MTP was −0.5° ± 1.5° (−2.9°–1.8°). The root-mean-square (RMS) error of these two PTS angles was 1.6° with this method. Conclusion Cartilage remnants, osteophyte formation and subchondral bone depression do not affect the direct referencing method in almost all knees for which medial UKA is indicated. When the posterior “high” osteophyte of the MTP is noted on preoperative radiography, preoperative MRI or CT scan is recommended to confirm no “high” osteophyte on the medial second quarter. The accuracy of this method seems equal to that of robotic-assisted surgery (the RMS error in previous reports, 1.6°–1.9°).