Kazumasa Miyatake

Mouse Synovial Mesenchymal Stem Cells Increase in yield with Knee Inflammation

Even though mouse studies have various advantages, harvesting an adequate number of synovial mesenchymal stem cells (MSCs) is difficult in mice. We investigated whether the total yield of MSCs increased in synovium with inflammation in mice. Infrapatellar fat pads (IFPs) were harvested from 10 knees of 5 mice 3, 7, and 14 days after intraarticular injection of carrageenan. Ten IFPs were also harvested from untreated knees as a control. Seven days after initial plating, the total yield of cells was compared among the 4 groups (n = 4–6). The harvested cells were analyzed for multipotentiality and surface epitopes. Furthermore, knee synovitis was compared among the 4 groups in histology. The number of cells in the 3 and 7 days treated group was significantly higher than the other groups. The harvested cells had characteristics of MSCs. Synovitis in the 3 and 7 days treated groups was significantly severer than the other groups. There seemed to be a relationship between the synovitis score and the total yield of cells derived from IFPs. In mice, it became possible to increase the yield 50‐fold by inducing inflammation. This method makes it possible to analyze the molecular mechanisms of cartilage regeneration of synovial MSCs in mice models.

Osteopontin Level in Synovial Fluid Is Associated with the Severity of Joint Pain and Cartilage Degradation after Anterior Cruciate Ligament Rupture

Objective To explore the molecular function of Osteopontin (OPN) in the pathogenesis of human OA, we compared the expression levels of OPN in synovial fluid with clinical parameters such as arthroscopic observation of cartilage damage and joint pain after joint injury. Methods Synovial fluid was obtained from patients who underwent anterior cruciate ligament (ACL) reconstruction surgery from 2009 through 2011 in our university hospital. The amounts of intact OPN (OPN Full) and it’s N-terminal fragment (OPN N-half) in synovial fluid from each patient were quantified by ELISA and compared with clinical parameters such as severity of articular cartilage damage (TMDU cartilage score) and severity of joint pain (Visual Analogue Scale and Lysholm score). Results Within a month after ACL rupture, both OPN Full and N-half levels in patient synovial fluid were positively correlated with the severity of joint pain. In contrast, patients with ACL injuries greater than one month ago felt less pain if they had higher amounts of OPN N-half in synovial fluid. OPN Full levels were positively correlated with articular cartilage damage in lateral tibial plateau. Conclusion Our data suggest that OPN Full and N-half have distinct functions in articular cartilage homeostasis and in human joint pain.

Elimination of BMP7 from the developing limb mesenchyme leads to articular cartilage degeneration and synovial inflammation with increased age

While osteo‐ and chondro‐inductive activities of recombinant human bone morphogenetic protein 7 are well established, evaluation of the role of endogenous BMP7 in skeletal homeostasis has been hampered by perinatal lethality in BMP7 knockout mice. Here, we examined physiological roles of endogenous BMP7 in joint homeostasis and showed that proteoglycan contents in articular cartilage were significantly reduced in the absence of BMP7. Loss of BMP7 did not affect survival of articular cartilage cells, but resulted in reduced expression of aggrecan and enhanced expression of matrix metalloproteinase 13. We also found extensive synovial hyperplasia and enhanced expression of Activin A. These findings suggest that locally produced BMP7 is prerequisite for postnatal synovial joint homeostasis and may be involved in osteoarthritic changes in adults.

Human YKL39 (chitinase 3-like protein 2), an osteoarthritis-associated gene, enhances proliferation and type II collagen expression in ATDC5 cells

Human YKL39 (chitinase 3-like protein 2/CHI3L2) is a secreted 39kDa protein produced by articular chondrocytes and synoviocytes. Recent studies showed that hYKL-39 expression is increased in osteoarthritic articular chondrocytes suggesting the involvement of hYKL-39 in the progression of osteoarthritis (OA). However little is known regarding the molecular function of hYKL-39 in joint homeostasis. Sequence analyses indicated that hYKL-39 has significant identity with the human chitotorisidase family molecules, although it is considered that hYKL-39 has no enzymatic activity since it lacks putative chitinase catalytic motif. In this study, to examine the molecular function of hYKL-39 in chondrocytes, we overexpressed hYKL-39 in ATDC5 cells. Here we report that hYKL-39 enhances colony forming activity, cell proliferation, and type II collagen expression in these cells. These data suggest that hYKL-39 is a novel growth and differentiation factor involved in cartilage homeostasis.

Comparison of Different Materials and Proximal Coatings Used for Femoral Components in One-Stage Bilateral Total Hip Arthroplasty

To evaluate the mid-term effects of different materials and coatings used for femoral components, we prospectively performed 21 one-stage bilateral total hip arthroplasties using 2 anatomical stems which have identical geometries, randomized to side. One stem was made of Ti6Al4V alloy and had a hydroxyapatite coating on grit-blasted surface proximally, and the other was made of TMZF™ alloy and had a proximal coating of hydroxyapatite in addition to an arc-deposited titanium surface coating. Although we found extensions of radiopaque lines to the surface of coatings of seven grit-blasted stems whereas we found none in the case of the arc-deposited titanium stems, all hips showed excellent clinical and radiological outcomes as shown by radiographs and bone mineral density at the final follow-up, average 5.5 years postoperatively.

Follistatin alleviates synovitis and articular cartilage degeneration induced by carrageenan.

Activins are proinflammatory cytokines which belong to the TGFβ superfamily. Follistatin is an extracellular decoy receptor for activins. Since both activins and follistatin are expressed in articular cartilage, we hypothesized that activin-follistatin signaling participates in the process of joint inflammation and cartilage degeneration. To test this hypothesis, we examined the effects of follistatin in a carrageenan-induced mouse arthritis model. Synovitis induced by intra-articular injection of carrageenan was significantly alleviated by preinjection with follistatin. Macrophage infiltration into the synovial membrane was significantly reduced in the presence of follistatin. In addition, follistatin inhibited proteoglycan erosion induced by carrageenan in articular cartilage. These data indicate that activin-follistatin signaling is involved in joint inflammation and cartilage homeostasis. Our data suggest that follistatin can be a new therapeutic target for inflammation-induced articular cartilage degeneration.

Comparison of wear rate and osteolysis between second-generation annealed and first-generation remelted highly cross-linked polyethylene in total hip arthroplasty. A case control study at a minimum of five years

BACKGROUND There is no previous report that directly compared wear resistance of second-generation annealed highly cross-linked polyethylene with that of first-generation remelted highly cross-linked polyethylene. We therefore performed a retrospective study at a minimum of 5-year follow-up comparing second-generation annealed and first-generation remelted highly cross-linked polyethylene in order to: (1) assess wear rates and (2) compare the incidence of osteolysis between, (3) identify the frequency of complication related to the two types of highly cross-linked polyethylene. HYPOTHESIS There is a difference in the linear wear rate and the incidence of osteolysis between the two types of highly cross-linked polyethylene in total hip arthroplasty. MATERIALS AND METHODS In a single centre study, we reviewed 123 primary cementless total hip arthroplasties between 2010 and 2011 that were performed with 32mm alumina ceramic on second-generation annealed (X3) or first-generation remelted (Longevity) highly cross-linked polyethylene liner. There was no specific reason for the choice of the type of highly cross-linked polyethylene. There were no significant differences between the two groups in respect of gender, diagnosis, body mass index, pre- and post-operative functional and activity score, cup size, and cup orientation except the younger age in the X3 group. The mean wear rate and the incidence of osteolysis were evaluated at the latest follow-up. RESULTS One hundred nine cases followed over 5 years post-operatively (88.6% in all consecutive cases) were evaluated. X3 and Longevity were used in 54 and 55 cases, respectively. The mean follow-up was 5.3 years in both groups. The mean linear wear rate of X3 and Longevity group was 0.045±0.023mm/year and 0.076±0.031mm/year, respectively (P<0.001). No osteolysis was found on plain X-rays in both groups and no specific complication was related to these highly cross-linked components. DISCUSSION Excellent wear resistance of both types of highly cross-linked polyethylene liner was revealed in our study. The difference of wear rate between two materials should be monitored in a longer follow-up. LEVEL OF EVIDENCE Level III retrospective case control study.