Manabu Tsukamoto

Fifteen-Year Comparison of Wear and Osteolysis Analysis for Cross-Linked or Conventional Polyethylene in Cementless Total Hip Arthroplasty for Hip Dysplasia—A Retrospective Cohort Study

BACKGROUND Cross-linked polyethylene (XLPE) acetabular liners used in cementless total hip arthroplasty (THA) have demonstrated better wear resistance at 10 years compared with conventional polyethylene (CPE) liners. No clinical studies have compared XPLE to CPE liners beyond 10 years. METHODS We performed a 15-year retrospective cohort study on cementless THA performed in patients with developmental hip dysplasia to measure the differences in polyethylene wear rates and the presence of osteolysis. Twenty-four THAs with XLPE and 17 THAs with CPE were evaluated. The mean age of patients was 55.9 years (41-68) in the XLPE group and 54.4 years (40-67) in the CPE group. The mean follow-up period was 15.1 years (13.9-16.1) in the XLPE group and 15.2 years (14.5-16.0) in the CPE group. RESULTS The XLPE group had a significantly lower wear rate at 5 and 10 years compared with the CPE group; however, no significant difference was found at 15 years (XLPE group, 0.040 mm/y; CPE group, 0.034 mm/y). In addition, the incidence of osteolysis did not differ significantly between the groups. However, the incidence of excessive wear between 10 and 15 years after surgery in the XLPE group was significantly higher than that in the CPE group. CONCLUSION XLPE demonstrated no advantage in the wear rate or the incidence of osteolysis at 15 years, despite having superior wear resistance up to 10 years. It is concerning that the incidence of excessive wear was higher in the XLPE group between 10 and 15 years, and this finding should alert the arthroplasty community to this possible problem with the more highly cross-linked polyethylene.

Isolation and Characterization of Synovial Mesenchymal Stem Cell Derived from Hip Joints: A Comparative Analysis with a Matched Control Knee Group

Purpose. To determine the characteristics of MSCs from hip and compare them to MSCs from knee. Methods. Synovial tissues were obtained from both the knee and the hip joints in 8 patients who underwent both hip and knee arthroscopies on the same day. MSCs were isolated from the knee and hip synovial samples. The capacities of MSCs were compared between both groups. Results. The number of cells per unit weight at passage 0 of synovium from the knee was significantly higher than that from the hip (P < 0.05). While it was possible to observe the growth of colonies in all the knee synovial fluid samples, it was impossible to culture cells from any of the hip samples. In adipogenesis experiments, the frequency of Oil Red-O-positive colonies and the gene expression of adipsin were significantly higher in knee than in hip. In osteogenesis experiments, the expression of COL1A1 and ALPP was significantly less in the knee synovium than in the hip synovium. Conclusions. MSCs obtained from hip joint have self-renewal and multilineage differentiation potentials. However, in matched donors, adipogenesis and osteogenesis potentials of MSCs from the knees are superior to those from the hips. Knee synovium may be a better source of MSC for potential use in hip diseases.

Elcatonin prevents bone loss caused by skeletal unloading by inhibiting preosteoclast fusion through the unloading-induced high expression of calcitonin receptors in bone marrow cells

This study aimed to clarify whether elcatonin (EL) has a preventive action on bone dynamics in skeletal unloading. Seven-week-old male C57BL/6J mice with either ground control (GC) or tail suspension (TS) were administered EL 20U/kg or a vehicle (veh) three times per week and assigned to one of the following four groups: GCEL, GCveh, TSEL, and TSveh. Blood samples and bilateral femurs and tibias of the mice were obtained for analysis. After 7days of unloading, the trabecular bone mineral density in the distal femur obtained via peripheral quantitative computed tomography and the trabecular bone volume were significantly higher in the TSEL group than in the TSveh group. The bone resorption histomorphometric parameters, such as the osteoclast surface and osteoclast number, were significantly suppressed in the TSEL mice, whereas the number of preosteoclasts was significantly increased. The plasma level of tartrate-resistant acid phosphatase-5b (TRACP-5b) was significantly lower in the TSEL group than in all other groups. In the bone marrow cell culture, the number of TRACP-positive (TRACP(+)) multinucleated cells was significantly lower in the TSEL mice than in the TSveh mice, whereas the number of TRACP(+) mononucleated cells was higher in the TSEL mice. On day 4, the expression of nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1 (NFATc1), cathepsin K and d2 isoform of vacuolar ATPase V0 domain (ATP6V0D2) mRNA in the bone marrow cells in the TSEL mice was suppressed, and the expression of calcitonin receptor (Calcr) mRNA on day 1 and Calcr antigen on day 4 were significantly higher in the TSveh mice than in the GCveh mice. EL prevented the unloading-induced bone loss associated with the high expression of Calcr in the bone marrow cells of mouse hindlimbs after tail suspension, and it suppressed osteoclast development from preosteoclasts to mature osteoclasts through bone-resorbing activity. This study of EL-treated unloaded mice provides the first in vivo evidence of a physiological role of EL in the inhibition of the differentiation process from preosteoclasts to osteoclasts.

Disruption of the Aldehyde Dehydrogenase 2 Gene Results in No Increase in Trabecular Bone Mass Due to Skeletal Loading in Association with Impaired Cell Cycle Regulation Through p21 Expression in the Bone Marrow Cells of Mice

Approximately 45% of people of East Asian descent have the inactive aldehyde dehydrogenase 2 (ALDH2) phenotype. The enzyme defect of ALDH2 has been found to adversely influence the risk of osteoporosis. The aim of this study was to clarify the effect of skeletal loading on trabecular bone structure and dynamics in Aldh2-disrupted mice in the absence of alcohol consumption. Four-week-old male Aldh2−/− (KO) and Aldh2+/+ (WT) mice were divided into a ground control (GC) group and a climbing exercise (CE) group in each genotype. The trabecular bone mineral density of the distal femur measured by peripheral quantitative computed tomography in the wild-type CE (WTCE) group was significantly higher than that in the wild-type GC (WTGC) group; however, there was no significant difference between the knockout CE (KOCE) and knockout GC (KOGC) groups. Bone histomorphometry revealed that osteogenic parameters were significantly increased in the WTCE group compared with the WTGC group, but not increased in the KOCE group compared with the KOGC group. Quantitative reverse transcriptase polymerase chain reaction and flow cytometry revealed that mRNA and protein expression levels of p21 were significantly decreased in the WTCE group compared with those in the WTGC group, while these differences were not observed between the KOGC and KOCE groups. This study provides the first in vivo evidence that p21 expression in the bone marrow is not decreased after skeletal loading and osteoblast differentiation is impaired in the absence of Aldh2 gene.

Findings as a starting point to unravel the underlying mechanisms of in vivo interactions involving Wnt10a in bone, fat and muscle

Wnt10a is a member of the WNT family. Although deficiency of this gene causes symptoms related to teeth, hair, nails, and skin, we recently demonstrated a new phenotype of Wnt10a knockout (KO) mice involving bone and fat. The in vivo effect of the Wnt10a gene on bone and fat is unclear, and the relationship between bone/fat and muscle in Wnt10a signaling is also interesting. We aimed to evaluate the tissue changes in Wnt10a KO mice compared to wild-type mice and show the findings as a starting point to unravel the underlying mechanisms of in vivo interactions involving Wnt10a in bone, fat and muscle. Trabecular bone loss in the lower limbs of Wnt10a mice and decreased bone mineralization were observed. The adipose tissue in bone marrow was also decreased, and adipocyte differentiation was reduced. The body fat mass in Wnt10a KO mice was decreased, and white adipocytes in subcutaneous fat were converted to beige adipocytes. The muscle weight of the lower limbs was not decreased despite trabecular bone loss, but Gdf8/myostatin expression was reduced in the subcutaneous fat and gastrocnemius muscles of Wnt10a KO mice. Thus, in vivo deletion of Wnt10a inhibited osteogenic activity, promoted beige adipogenesis of white adipocytes and maintained muscle mass. These results suggest that regulation of Gdf8 by Wnt10a may help maintain the muscle mass of Wnt10a KO mice. This study was the first to histologically evaluate the bone, fat and muscle phenotypes of Wnt10a KO mice. The results of this study, which were obtained by investigating the three tissues together, could influence the understanding of in vivo interactions involving the Wnt10a gene.

Systemic bone loss, impaired osteogenic activity and type I muscle fiber atrophy in mice with elastase-induced pulmonary emphysema: Establishment of a COPD-related osteoporosis mouse model

Although it is suggested that chronic obstructive pulmonary disease (COPD) and bone are related, almost all of the pathological mechanisms of COPD-related osteoporosis remain unknown. There is a mouse model showing a deterioration of bone quality after cigarette smoke exposure; however, in smoking exposure models, various factors exist that affect bone metabolism, such as smoking and body weight loss (muscle and fat mass loss). We considered it appropriate to use an elastase-induced emphysema model to exclude factors influencing bone metabolism and to investigate the influence of pulmonary emphysema on bone metabolism. The purpose of this study was to establish a COPD/emphysema-related osteoporosis mouse model by using the elastase-induced emphysema model. The lumbar vertebrae and femurs/tibiae exhibited trabecular bone loss and impaired osteogenic activity in 24-week-old male elastase-induced emphysema model mice. In addition, the model mice showed atrophy of type I muscle fibers without atrophy of type II muscle fibers. We believe that the mice described in this experimental protocol will be accepted as a COPD/emphysema-related osteoporosis mouse model and contribute to further investigations.

Correction to: Microstructure of osteophytes in medial knee osteoarthritis

The above article originally published with an error present in Table 2 and is now presented correctly in this article.

Microstructure of osteophytes in medial knee osteoarthritis

Knee osteoarthritis (OA) is one of the most common musculoskeletal diseases and osteophytes area frequent radiographic feature of knee OA. The osteophyte structure in knee OA, however, is not well elucidated. This study aimed to clarify the three-dimensional microstructural characteristics of osteophytes in the medial compartment of the knee in knee OA patients using micro-computed tomography (micro-CT). We hypothesized that the morphology of osteophytes would differ from that of the neighboring normal cancellous bones. Ten medial compartment knee OA patients with Kellgren-Lawrence grade 4 severity were enrolled in the study, and all patients underwent total knee arthroplasty. Osteophytes and cancellous bones were obtained from the medial femoral condyle. The three-dimensional trabecular bone microstructure was analyzed by quantitative micro-CT using image analysis software. The trabecular bone volume fraction and trabecular number were significantly lower in osteophytes than in cancellous bones. Consistently, trabecular separation was significantly higher in osteophytes. Osteophytes exhibited disorganized trabecular orientation, trabecular perforation, disruption, and complete disconnection. These findings suggest that osteophytes are functionally fragile.

Cortical bone loss due to skeletal unloading in aldehyde dehydrogenase 2 gene knockout mice is associated with decreased PTH receptor expression in osteocytes

Aldehyde dehydrogenase 2 (ALDH2) is the enzyme that degrades and detoxifies the acetaldehyde produced by alcohol metabolism. In our previous study, we found that compared with wild-type mice (WT), climbing exercises did not increase trabecular bone mass in Aldh2 knockout mice (KO). The purpose of this study was to clarify the effect of the Aldh2 gene on cortical bone structure and on the dynamics of skeletal unloading. Eight-week-old male KO and WT were divided into ground control (GC) or tail suspension (TS) groups for one week (i.e., the KOGC, KOTS, WTGC and WTTS groups). We measured the bone mineral density (BMD) of the femur using dual-energy X-ray absorptiometry. We assessed the femoral morphometry using peripheral quantitative computed tomography (pQCT) and evaluated the femoral cortex histomorphometry, and cortical mRNA using quantitative RT-PCR and cortical bone immunohistostaining. No significant differences were found between the femoral BMD of WTGC and that of WTTS, but the BMD in KOTS was significantly lower than that of KOGC. The pQCT results revealed that the cortical BMD of the femoral diaphysis in KOTS was significantly lower than that of KOGC. Furthermore, the cortical bone area and cortical thickness were significantly lower in KOTS than in the other three groups. Cortical histomorphometric analysis revealed that the endosteal and periosteal bone formation parameters were significantly lower in KOTS than in KOGC. Bone formation signals such as parathyroid hormone receptor (PTHR) were significantly decreased in KOTS compared with the levels in KOGC. Cortical bone immunohistostaining revealed a significantly decreased expression of PTHR in the osteocytes of KOTS compared with the expression level in KOGC. Thus, we concluded that when the Aldh2 gene is disrupted, skeletal unloading suppresses bone formation to decrease cortical bone mass, which may be mediated by a decreased expression of PTH receptors in osteocytes.

Highly cross-linked polyethylene in total hip arthroplasty, present and future

Excessive polyethylene wear after total hip arthroplasty using non-cross-linked ultra-high-molecular-weight polyethylene (UHMWPE) is known to cause osteolysis followed by implant loosening (1,2). To reduce the amount of wear, several manufacturers have attempted to modify bearing surface materials. Highly cross-linked polyethylene (HXLPE) was utilized the processes of gamma or electron beam radiation, to increase the degree of crosslinking within the material. Re-melting process would take on to reduce the amount of oxidation involving to crosslink. As a result, it is expected that wear resistance of the polyethylene increase.