CITED2 mediates the mechanical loading-induced suppression of adipokines in the infrapatellar fat pad.

Adipokines secreted from the infrapatellar fat pad (IPFP), such as adipsin and adiponectin, have been implicated in osteoarthritis pathogenesis. CITED2, a mechanosensitive transcriptional regulator with chondroprotective activity, may modulate their expression. Cited2 haploinsufficient mice (Cited2+/- ) on a high-fat diet (HFD) exhibited increased body weight and increased IPFP area compared to wild-type (WT) mice on an HFD. While an exercise regimen of moderate treadmill running induced the expression of CITED2, as well as PGC-1α, and reduced the expression of adipsin and adiponectin in the IPFP of WT mice on an HFD, Cited2 haploinsufficiency abolished the loading-induced expression of PGC-1α and loading-induced suppression of adipsin and adiponectin. Furthermore, knocking down or knocking out CITED2 in adipose stem cells (ASCs)/preadipocytes derived from the IPFP in vitro led to the increased expression of adipsin and adiponectin and reduced PGC-1α, and abolished the loading-induced suppression of adipsin and adiponectin and loading-induced expression of PGC-1α. Overexpression of PGC-1α in these ASC/preadipocytes reversed the effects caused by CITED2 deficiency. The current data suggest that CITED2 is a critical regulator in physiologic loading-induced chondroprotection in the context of an HFD and PGC-1α is required for the inhibitory effects of CITED2 on the expression of adipokines such as adipsin and adiponectin in the IPFP.

Correction to: Green tea polyphenol treatment is chondroprotective, anti-inflammatory and palliative in a mouse posttraumatic osteoarthritis model.

Following publication of the original article [1], the authors reported an error in Figs. 2C and 5C.

Procyanidins Mitigate Osteoarthritis Pathogenesis by, at Least in Part, Suppressing Vascular Endothelial Growth Factor Signaling.

Procyanidins are a family of plant metabolites that have been suggested to mitigate osteoarthritis pathogenesis in mice. However, the underlying mechanism is largely unknown. This study aimed to determine whether procyanidins mitigate traumatic injury-induced osteoarthritis (OA) disease progression, and whether procyanidins exert a chondroprotective effect by, at least in part, suppressing vascular endothelial growth factor signaling. Procyanidins (extracts from pine bark), orally administered to mice subjected to surgery for destabilization of the medial meniscus, significantly slowed OA disease progression. Real-time polymerase chain reaction revealed that procyanidin treatment reduced expression of vascular endothelial growth factor and effectors in OA pathogenesis that are regulated by vascular endothelial growth factor. Procyanidin-suppressed vascular endothelial growth factor expression was correlated with reduced phosphorylation of vascular endothelial growth factor receptor 2 in human OA primary chondrocytes. Moreover, components of procyanidins, procyanidin B2 and procyanidin B3 exerted effects similar to those of total procyanidins in mitigating the OA-related gene expression profile in the primary culture of human OA chondrocytes in the presence of vascular endothelial growth factor. Together, these findings suggest procyanidins mitigate OA pathogenesis, which is mediated, at least in part, by suppressing vascular endothelial growth factor signaling.

Curcumin slows osteoarthritis progression and relieves osteoarthritis-associated pain symptoms in a post-traumatic osteoarthritis mouse model.

BACKGROUND: Curcumin has been shown to have chondroprotective potential in vitro. However, its effect on disease and symptom modification in osteoarthritis (OA) is largely unknown. This study aimed to determine whether curcumin could slow progression of OA and relieve OA-related pain in a mouse model of destabilization of the medial meniscus (DMM). METHODS: Expression of selected cartilage degradative-associated genes was evaluated in human primary chondrocytes treated with curcumin and curcumin nanoparticles and assayed by real-time PCR. The mice subjected to DMM surgery were orally administered curcumin or topically administered curcumin nanoparticles for 8 weeks. Cartilage integrity was evaluated by Safranin O staining and Osteoarthritis Research Society International (OARSI) score, and by immunohistochemical staining of cleaved aggrecan and type II collagen, and levels of matrix metalloproteinase (MMP)-13 and ADAMTS5. Synovitis and subchondral bone thickness were scored based on histologic images. OA-associated pain and symptoms were evaluated by von Frey assay, and locomotor behavior including distance traveled and rearing. RESULTS: Both curcumin and nanoparticles encapsulating curcumin suppressed mRNA expression of pro-inflammatory mediators IL-1ß and TNF-α, MMPs 1, 3, and 13, and aggrecanase ADAMTS5, and upregulated the chondroprotective transcriptional regulator CITED2, in primary cultured chondrocytes in the absence or presence of IL-1ß. Oral administration of curcumin significantly reduced OA disease progression, but showed no significant effect on OA pain relief. Curcumin was detected in the infrapatellar fat pad (IPFP) following topical administration of curcumin nanoparticles on the skin of the injured mouse knee. Compared to vehicle-treated controls, topical treatment led to: (1) reduced proteoglycan loss and cartilage erosion and lower OARSI scores, (2) reduced synovitis and subchondral plate thickness, (3) reduced immunochemical staining of type II collagen and aggrecan cleavage epitopes and numbers of chondrocytes positive for MMP-13 and ADAMTS5 in the articular cartilage, and (4) reduced expression of adipokines and pro-inflammatory mediators in the IPFP. In contrast to oral curcumin, topical application of curcumin nanoparticles relieved OA-related pain as indicated by reduced tactile hypersensitivity and improved locomotor behavior. CONCLUSION: This study provides the first evidence that curcumin significantly slows OA disease progression and exerts a palliative effect in an OA mouse model.

Optimal Irrigation and Debridement of Infected Total Joint Implants with Chlorhexidine Gluconate.

Previous study at our institution demonstrated that scrubbing a methicillin-resistant Staphylococcus aureus (MRSA)-coated titanium disk with chlorhexidine gluconate (CG) solution achieved superior biofilm eradication compared to alternative solutions. The current study aimed to identify the minimum CG concentration for effective bacteria eradication of an in vitro periprosthetic joint infection (PJI) model. MRSA colony-forming units (CFUs) were counted following simulated irrigation and debridement with varying CG solutions before and after a 24-hour reincubation period. Significant decrease was noted on all disks before reincubation. Postreincubation, significant decrease in CFUs was found in the 4% and 2% groups. This study demonstrated that I+D of an infected PJI model with 4% CG solution was effective at treating MRSA biofilm at concentrations as low as 2%.

Atypical Vancouver Type-C Periprosthetic Fracture Complicated by Nonunion: A Case Report.

CASE: In recent years, atypical femoral fractures (AFFs) associated with bisphosphonate use have increasingly been reported, but current definitions limit their diagnosis to native femora. Atypical periprosthetic fractures are rare. We present a case of a Vancouver type-C periprosthetic fracture that was recognized as an AFF following nonunion. CONCLUSION: Bisphosphonate-associated AFFs can present as periprosthetic fractures. Delayed recognition of the role of bisphosphonates in a periprosthetic fracture may lead to a worse outcome, including a delay in diagnosis, delayed union, and failure of fixation.

Green tea polyphenol treatment is chondroprotective, anti-inflammatory and palliative in a mouse post-traumatic osteoarthritis model.

INTRODUCTION: Epigallocatechin 3-gallate (EGCG), a polyphenol present in green tea, was shown to exert chondroprotective effects in vitro. In this study, we used a post-traumatic osteoarthritis (OA) mouse model to test whether EGCG could slow the progression of OA and relieve OA-associated pain. METHODS: C57BL/6 mice were subjected to surgical destabilization of the medial meniscus (DMM) or sham surgery. EGCG (25 mg/kg) or vehicle control was administered daily for four or eight weeks by intraperitoneal injection starting on the day of surgery. OA severity was evaluated by Safranin O staining and Osteoarthritis Research Society International (OARSI) score, and by immunohistochemical analysis to detect cleaved aggrecan and type II collagen, and expression of proteolytic enzymes matrix metalloproteinase (MMP)-13 and A Disintegrin And Metalloproteinase with Thrombospondin Motifs (ADAMTS5). Real-time polymerase chain reaction (PCR) was performed to characterize the expression of genes critical for articular cartilage homeostasis. During the course of the experiments, tactile sensitivity testing (von Frey test) and open field assays were used to evaluate pain behaviors associated with OA, and expression of pain expression markers and inflammatory cytokines in the dorsal root ganglion (DRG) were determined by real-time PCR. RESULTS: Four and eight weeks after DMM surgery, the cartilage in EGCG-treated mice exhibited less Safranin O loss and cartilage erosion, and lower OARSI scores compared to vehicle-treated controls, which was associated with reduced staining for aggrecan and type II collagen cleavage epitopes, and reduced staining for MMP-13 and ADAMTS5 in the articular cartilage. Articular cartilage in the EGCG-treated mice also exhibited reduced levels of MMP-1, -3, -8, -13, ADAMTS5, interleukin (IL)-1ß, and tumor necrosis factor (TNF)-α mRNA and elevated gene expression of the MMP regulator Cbp/p300 Interacting Transactivator 2 (CITED2). Compared to vehicle controls, mice treated with EGCG exhibited reduced OA-associated pain, as indicated by higher locomotor behavior (i.e. distance traveled). Moreover, expression of chemokine receptor (CCR2), and pro-inflammatory cytokines IL-1ß and TNF-α in the DRG were significantly reduced to levels similar to sham-operated animals. CONCLUSIONS: This study provides the first evidence in an OA animal model that EGCG significantly slows OA disease progression and exerts a palliative effect.

Knee arthrotomy closure with barbed suture in flexion versus extension: a porcine study.

The purpose of this biomechanical study was to evaluate knee arthrotomy closure with a barbed suture in flexion versus extension. 48 porcine knees were randomized into three groups: full extension, 30° flexion, and 60° flexion. Each knee was then flexed to 90° and then 120°, with failures recorded. Arthrotomy closure in extension had significantly higher failure rates (6/16) upon flexion to 90° compared to arthrotomy closure in either 30° or 60° flexion (0/32) (P = 0.032). Upon ranging from 0° to 120°, arthrotomy failure occurred in 50% (8/16) of arthrotomies in the extension group, 6.25% (1/16) in the 30° flexion group and 18.75% (3/16) in the 60° flexion group (P = 0.022). Knee arthrotomy closure in extension compared to flexion had significantly higher rates of failure.

Nutraceuticals: potential for chondroprotection and molecular targeting of osteoarthritis.

Osteoarthritis (OA) is a degenerative joint disease and a leading cause of adult disability. There is no cure for OA, and no effective treatments which arrest or slow its progression. Current pharmacologic treatments such as analgesics may improve pain relief but do not alter OA disease progression. Prolonged consumption of these drugs can result in severe adverse effects. Given the nature of OA, life-long treatment will likely be required to arrest or slow its progression. Consequently, there is an urgent need for OA disease-modifying therapies which also improve symptoms and are safe for clinical use over long periods of time. Nutraceuticals-food or food products that provide medical or health benefits, including the prevention and/or treatment of a disease-offer not only favorable safety profiles, but may exert disease- and symptom-modification effects in OA. Forty-seven percent of OA patients use alternative medications, including nutraceuticals. This review will overview the efficacy and mechanism of action of commonly used nutraceuticals, discuss recent experimental and clinical data on the effects of select nutraceuticals, such as phytoflavonoids, polyphenols, and bioflavonoids on OA, and highlight their known molecular actions and limitations of their current use. We will conclude with a proposed novel nutraceutical-based molecular targeting strategy for chondroprotection and OA treatment.

The use of dermabond® as an adjunct to wound closure after total knee arthroplasty: examining immediate post-operative wound drainage.

Wound drainage after total knee arthroplasty (TKA) can be detrimental to surgical outcome. This IRB-approved randomized, prospective, blinded study examined the use of Dermabond® as an adjunct to wound closure after TKA. We proposed that Dermabond® supplementation to wound closure would result in a significant decrease in wound drainage after TKA. After standardized closure, patients were randomized into experimental or control groups with the experimental group receiving Dermabond® supplementation. Standardized dressings were evaluated postoperatively and drainage units were compared using a Mann-Whitney U Test. The median drainage for the Dermabond group (153) was lower than the drainage for the control group (657) at a statistically significant level (P<0.001).

Histologic retrieval analysis of a porous tantalum metal implant in an infected primary total knee arthroplasty.

Porous tantalum (Zimmer, Inc, Warsaw, Ind) has the theoretical advantage of improved biologic fixation because of its high porosity, interconnected pore space, and modulus of elasticity. We present a case report documenting the retrieval and bone ingrowth analysis of a porous tantalum tibial component in an infected total knee arthroplasty. Results demonstrated a significantly larger amount of bone ingrowth present in the tibial posts (36.7%) when compared with the bone ingrowth into the tibial baseplate (4.9%) (P < .001). The data suggest that bone ingrowth seen in the plugs as well as baseplate was suggestive of viable bone tissue with healthy bone marrow, osteocytes, and lamella, resulting in a well-fixed tibial implant even at revision surgery for an infected total knee arthroplasty.

Unipolar vs bipolar hemostasis in total knee arthroplasty: a prospective randomized trial.

The purpose of this study was to investigate whether unipolar or bipolar hemostasis is more effective in reducing blood loss associated with primary total knee arthroplasty. We randomized 113 consecutive patients undergoing primary total knee arthroplasty into unipolar and bipolar hemostasis treatment groups. The mean postoperative drain output in the unipolar group was 776.5 mL compared with 778.7 mL and was not statistically significant (P = .97). There were no statistically significant differences in postoperative day 1 through 3 hemoglobin level (P = .2-.6) or hematocrit (P = .17-.46) values. The transfusion requirement in the unipolar group was 36% and 40% in the bipolar group (P = .67). Use of bipolar sealer compared with standard unipolar electrocauterization showed no significant difference in postoperative drain output, postoperative hemoglobin level and hematocrit values, or transfusion requirements.

Optimal irrigation and debridement of infected joint implants: an in vitro methicillin-resistant Staphylococcus aureus biofilm model.

Acute postoperative and acute, late hematogenous prosthetic joint infections have been treated with 1-stage irrigation and debridement with polyethylene exchange. Success rates, however, are highly variable. Reported studies demonstrate that detergents are effective at decreasing bacterial colony counts on orthopedic implants. Our hypothesis is that the combination of a detergent and an antiseptic would be more effective than using a detergent alone to decrease colony counts from a methicillin-resistant Staphylococcus aureus biofilm-coated titanium alloy disk simulating an orthopedic implant. In our study of various agents tested, chlorhexidine gluconate scrub (antiseptic and detergent) was the most effective at decreasing bacterial colony counts both prereincubation and postreincubation of the disks; pulse lavage and scrubbing were not more effective than pulse lavage alone.