Fermentation supernatant of Staphylococcus aureus drives catabolism in chondrocytes via NF-κB signaling mediated increase of cholesterol metabolism.

Septic arthritis induced by Staphylococcus aureus (S. aureus) causes irreversible cartilage degradation and subsequent permanent joint dysfunction. Recently, cartilage degradation in osteoarthritis is recognized to be associated with metabolic disorders. However, whether cholesterol metabolism is linked to septic arthritis pathology remains largely unknown. Here, we found that exposure to fermentation supernatant (FS) of S. aureus in chondrocytes resulted in a significant increase in expression of key modulators involved in cholesterol metabolism, including lectin-type oxidized low density lipoprotein receptor 1 (LOX1), cholesterol 25-hydroxylase (CH25H), 25- hydroxycholesterol 7α-hydroxylase (CYP7B1) as well as retinoic acid-related orphan receptor alpha (RORα), a binding receptor for cholesterol metabolites. We further demonstrated that enhancement of CH25H/CYP7B1/RORα axis resulted from FS exposure was mediated by activation of NF-κB signaling, along with upregulation in catabolic factors including matrix metallopeptidases (MMP3 and MMP13), aggrecanase-2 (ADAMTS5), and nitric oxide synthase-2 (NOS2) in chondrocytes. Exogenous cholesterol acts synergistically with FS in activating NF-κB pathway and increases cholesterol metabolism. While, the addition of tauroursodeoxycholic acid (TUDCA) which promotes cholesterol efflux, resulted in remarkable reduction of intracellular cholesterol level and restoration of balance between anabolism and catabolism in FS treated chondrocytes. Collectively, our data indicated that, in response to FS of S. aureus, NF-κB signaling activation coupled with increased cholesterol metabolism to stimulate catabolic factors in chondrocytes, highlighting cholesterol metabolism as a potential therapeutic target for treating septic arthritis.

Etoposide-mediated depletion of peripheral blood monocytes post s.aureus infection attenuates septic arthritis by modulating macrophage-derived factors responsible for inflammatory destruction.

S.aureus induced septic arthritis remains a serious medical concern due to its rapidly progressive disease profile. The multidrug resistant nature of S.aureus demands the development of new strategies for the treatment of S.aureus arthritis. Since monocyte/macrophage population has been recognized as an important axis in joint inflammation and destruction, selective depletion of peripheral blood monocytes might influence the outcome and progression of the disease. Therefore, in this study we have put forward the concept of monocyte depletion by using etoposide, a drug that selectively depletes the monocyte/macrophage population. Mice were inoculated with live S.aureus for the development of septic arthritis. Post S.aureus infection, etoposide was subcutaneously injected. The severity of arthritis was found to be significantly low in the etoposide treated mice throughout the course. Arthritis index, histopathological analysis and TRAP staining images confirmed effectiveness of etoposide treatment in regulating inflammation and bone cartilage destruction. Lower levels of inflammatory cytokines, ROS, MMP-2, RANKL, OPN and plasmin reflected less severe arthritic destruction after etoposide treatment in arthritic mice. The bacterial load was not increased after etoposide treatment. Together, the presented data suggested that monocyte depletion by etoposide might represent an alternative therapeutic strategy for the treatment of S.aureus arthritis.

A reliable method to avoid contamination during cartilage graft preparation in septorhinoplasty.

PURPOSE: The aim of the study is to determine the risk of contamination in the cartilage graft materials prepared on the swester table and those prepared in a sterile package, and to reveal a more reliable method by performing the microbiological examination of these materials. METHODS: Cartilages removed from the nasal septum were divided into four pieces. The first part (Sample A) was directly placed into the medium. Sample B was prepared by being crushed in a sterile package. Sample C was prepared on the auxiliary swester table, and Sample D was prepared on the main swester table actively used by surgery team. All samples were transferred in a 1 ml brain heart(BH) liquid medium. From each BH medium, 100 µl culture was performed on blood agar, eosin-methylene blue-lactose-sucrose agar and chocolate agar. RESULTS: Bacterial growth was detected in 2 of the samples A, in 4 of the samples B, in 24 of the samples C, and in 36 of the samples D. The number of patients with bacterial growth in the samples C and/or D despite no growth in the sample B was 35. When the samples A/B and C/D were compared in terms of bacterial growth, a significant difference was found in all matchings (p < 0.001 for all comparisons).  CONCLUSION: These findings showed that preparation of the cartilage grafts on the swester table was extremely risky for microbiological contamination. Arslan and his colleagues suggest that preparing a graft material in a sterile package is extremely simple, cheap, and it also reduces contamination risk significantly.

Downregulation of PHEX in multibacillary leprosy patients: observational cross-sectional study.

BACKGROUND: Peripheral nerve injury and bone lesions, well known leprosy complications, lead to deformities and incapacities. The phosphate-regulating gene with homologies to endopeptidase on the X chromosome (PHEX) encodes a homonymous protein (PHEX) implicated in bone metabolism. PHEX/PHEX alterations may result in bone and cartilage lesions. PHEX expression is downregulated by intracellular Mycobacterium leprae (M. leprae) in cultures of human Schwann cells and osteoblasts. M. leprae in vivo effect on PHEX/PHEX is not known. METHODS: Cross-sectional observational study of 36 leprosy patients (22 lepromatous and 14 borderline-tuberculoid) and 20 healthy volunteers (HV). The following tests were performed: PHEX flow cytometric analysis on blood mononuclear cells, cytokine production in culture supernatant, 25-hydroxyvitamin D (OHvitD) serum levels and (99m)Tc-MDP three-phase bone scintigraphy, radiography of upper and lower extremities and blood and urine biochemistry. RESULTS: Significantly lower PHEX expression levels were observed in lepromatous patients than in the other groups (χ(2) = 16.554, p < 0.001 for lymphocytes and χ(2) = 13.933, p = 0.001 for monocytes). Low levels of 25-(OHvitD) were observed in HV (median = 23.0 ng/mL) and BT patients (median = 27.5 ng/mL) and normal serum levels were found in LL patients (median = 38.6 ng/mL). Inflammatory cytokines, such as TNF, a PHEX transcription repressor, were lower after stimulation with M. leprae in peripheral blood mononuclear cells from lepromatous in comparison to BT patients and HV (χ(2) = 10.820, p < 0.001). CONCLUSION: Downregulation of PHEX may constitute an important early component of bone loss and joint damage in leprosy. The present results suggest a direct effect produced by M. leprae on the osteoarticular system that may use this mechanism.

Evaluating portable wire-flooring models for inducing bacterial chondronecrosis with osteomyelitis in broilers.

Rearing broilers on flat or sloping wire flooring is an effective method for consistently triggering lameness attributable to bacterial chondronecrosis with osteomyelitis (BCO). Portable obstacles known as speed bumps (SB) also consistently trigger modest incidences of BCO when they are installed between feed and water lines in litter flooring facilities. Two experiments were conducted to determine the most effective broiler age for introducing the SB into litter flooring pens, and to evaluate alternative configurations of the traditional SB with the expectation that amplified mechanical challenges to the legs of broilers should increase the incidence of BCO. Broiler chicks obtained from commercial hatcheries (lines B and D in experiment 1, lines A and B in experiment 2) were reared in floor pens with ad libitum feed and water and a 23L:1D photoperiod. In experiment 1, the 5 floor treatments included wood shavings litter only (L), flat wire only (W), or litter plus SB installed at 14, 28, or 42 d of age. Line B was more susceptible to lameness than line D (25.9 vs. 15.3% for all treatments combined; P = 0.001). Both lines developed low incidences of lameness on L (11 to 13%), intermediate incidences on SB regardless of day of installation (12 to 23%), and high incidences on W (21 to 39%). In experiment 2, broilers were reared with 7 floor treatments, including L, W, SB with a 50% slope (SB50%); SB50% with a limbo bar installed over the apex; SB with a 66% slope and limbo bar; SB50% with a nipple water line suspended over the apex; and a pagoda-top SB. All SB were inserted on d 28. Line B was more susceptible to lameness than line A (20.2 vs. 16.1% for all treatments combined; P < 0.05), and for both lines combined the lameness percentages averaged 7.7 (L), 29.2 (W), 17.3 (SB50%), 16.2 (SB50% with a limbo bar), 21.5 (SB with a 66% slope and limbo bar), 20.8 (SB50% with a nipple water line), and 11.5% (pagoda-top). These studies demonstrate the portable SB can be effectively used to experimentally trigger BCO in broilers.

Bacterial chondronecrosis with osteomyelitis in broilers: influence of sires and straight-run versus sex-separate rearing.

Two experiments (E1, E2) were conducted to compare the influence of sires (sire A on dam C vs. sire B on dam C) and straight-run versus sex-separate rearing on the incidence of bacterial chondronecrosis with osteomyelitis (BCO) in broilers. Fertile eggs from commercial breeder flocks were incubated and hatched at the University of Arkansas Poultry Research Hatchery. Male and female chicks were reared together (straight-run) or separately (sex-separate) in 3 × 3 m pens on litter or flat wire flooring with 65 (E1) or 60 (E2) birds per pen. Necropsies revealed lesions that are pathognomonic for BCO in ≥98% of the birds that became lame. The SigmaStat Z-test was used to compare cumulative BCO incidences through 8 wk of age. For birds reared on litter, the incidences of BCO were low regardless of cross or sex (range: 1.7 to 5.1%; P ≥ 0.6). Within a cross and sex, rearing the broilers straight-run versus sex-separate on wire flooring did not significantly affect the incidence of BCO. Significant incidences of BCO did not develop until after d 40. Males from the sire A cross developed a higher incidence of BCO than males from the sire B cross in E1 (27 vs. 17%, respectively; P = 0.009) but not in E2 (28.5 vs. 22.6%, respectively; P = 0.141). In both experiments, males from the sire A cross developed higher incidences of BCO than females from the sire B cross (27 vs. 11.9%, in E1; 28.5 vs. 14.8%, in E2). With the sexes pooled, broilers from the sire A cross consistently developed higher incidences of BCO than broilers from the sire B cross (21.4 vs. 14.9%, P = 0.005 in E1; 26.5 vs. 18.7%, P = 0.003 in E2). High susceptibilities to both femoral head (all femoral head necrosis = 66 to 85% incidences) and tibial head (all tibial head necrosis = 81 to 96% incidences) BCO lesions were demonstrated in lame birds from both sexes and crosses. This study supports a sire influence on the susceptibility of broilers to BCO. Sire lines can be chosen to reduce BCO susceptibility when broilers are grown beyond 6 wk of age.

Sterilizing tissue-materials using pulsed power plasma.

This paper investigates the potential of pulsed power to sterilize hard and soft tissues and its impact on their physico-mechanical properties. It hypothesizes that pulsed plasma can sterilize both vascular and avascular tissues and the transitive layers in between without deleterious effects on their functional characteristics. Cartilage/bone laminate was chosen as a model to demonstrate the concept, treated at low temperature, at atmospheric pressure, in short durations and in buffered environment using a purposed-built pulsed power unit. Input voltage and time of exposure were assigned as controlling parameters in a full factorial design of experiment to determine physical and mechanical alteration pre- and post-treatment. The results demonstrated that, discharges of 11 kV sterilized samples in 45 s, reducing intrinsic elastic modules from 1.4 ± 0.9 to 0.9 ± 0.6 MPa. There was a decrease of 14.1 % in stiffness and 27.8 % in elastic-strain energy for the top quartile. Mechanical impairment was directly proportional to input voltage (P value < 0.05). Bacterial inactivation was proportional to treatment time for input voltages above 32 V (P < 0.001; R Sq = 0.98). Thermal analysis revealed that helix-coil transition decelerated with exposure time and collagen fibrils were destabilized as denaturation enthalpy reduced by 200 µV. We concluded by presenting a safe operating threshold for pulsed power plasma as a feasible protocol for effective sterilization of connective tissues with varying level of loss in mechanical robustness which we argue to be acceptable in certain medical and tissue engineering application.

Susceptibility of 4 commercial broiler crosses to lameness attributable to bacterial chondronecrosis with osteomyelitis.

Growing broilers on wire flooring provides an excellent experimental model for exposing susceptibility to lameness attributable to bacterial chondronecrosis with osteomyelitis (BCO). Two independent experiments (E1, E2) were designed to compare the susceptibilities of broilers from 4 commercial crosses (W, X, Y, and Z). The standard crosses (W and Y) grow rapidly at an early age, whereas high-yield crosses (X and Z) initially tend to grow more slowly. Chicks were obtained from a commercial hatchery for E1, or were hatched at the University of Arkansas Poultry Research Hatchery for E2. Males and females were reared together (E1; n = 360/cross) or separately (E2; n = 390/cross) in 3 × 3 m pens on litter or wire flooring (wire). Necropsies revealed lesions that were pathognomonic for BCO in ≥94% of the birds that became lame. The SigmaStat Z-test was used to compare cumulative lameness incidences at 8 wk of age. For birds reared on litter, lameness incidences were low and did not differ between crosses or sexes (range: 2.2 to 4.6%; P ≥ 0.6). When males were reared on wire, their lameness incidences (by cross) were E1 = 52% for W(b); 42% for X(c); 69% for Y(a), and 44% for Z(bc); E2 = 31% for W(b); 19% for X(c); 49% for Y(a); and 25% for Z(bc). For females reared on wire, the lameness incidences were E1 = 40% for W(b), 30% for X(c), 49% for Y(a), and 28% for Z(c); E2 = 16% for W; 15% for X; 16% for Y; and 15% for Z (ns). Accordingly, the hierarchical ranking for BCO susceptibility by broiler cross was X ≤ Z ≤ W < Y for males in E1 and E2, for females in E1, and for males and females pooled in E1 and E2. Standard broiler crosses developed higher incidences of lameness than high-yield crosses, implicating an association between rapid early growth and susceptibility to BCO. Rearing the females separately on wire in E2 led to uniformly low incidences of BCO, regardless of cross. Stress-mediated immunosuppression contributes to the pathogenesis of BCO; perhaps female broilers experience less social or competitive stress when reared separately from their male hatch mates.

Risk factors for nasopharyngeal carriage of Streptococcus pneumoniae in healthy Turkish children after the addition of heptavalent pneumococcal conjugate vaccine (PCV7) to the national vaccine schedule.

The purpose of this study was to investigate the effects of pneumococcal conjugate vaccine (PCV7) on nasopharyngeal (NP) carriage rates of Streptococcus pneumoniae in healthy Turkish children. The study was conducted on 1101 healthy Turkish children between 1 month and 18 years of age. The median and mean ages of the children were 25 months (1 month-18 years) and 45.7±49.6 months, respectively. S. pneumoniae was isolated in 241/1101 (21.9%) children included in the study. According to multivariate analysis, being <5 years of age, presence of a child attending a daycare center, recovery from respiratory infection within the last month, low income level of the family, and presence of more children in the family were found to be the risk factors for the NP pneumococcal carriage. The carriage rate of NP pneumococci in healthy children was not influenced by PCV7 in Turkey.

Remains of infection.

In Lyme disease, musculoskeletal symptoms can persist after treatment, which has led to the hypothesis that the causal organism itself may escape antibiotic therapy. The controversy that surrounds this question extends beyond patients, physicians, and scientists, as public health organizations struggle with how the disease should be diagnosed and treated. Is Lyme disease an infection that resolves, or is the spirochetal agent resilient and evasive? In this issue of the JCI, Bockenstedt et al. address this issue and present compelling evidence that the residues of nonviable spirochetes can persist in cartilaginous tissue long after treatment and may contribute to antibiotic-refractory Lyme arthritis.

Spirochete antigens persist near cartilage after murine Lyme borreliosis therapy.

An enigmatic feature of Lyme disease is the slow resolution of musculoskeletal symptoms that can continue after treatment, with some patients developing an inflammatory arthritis that becomes refractory to antibiotic therapy. Using intravital microscopy and the mouse model of Lyme borreliosis, we observed that Borrelia burgdorferi antigens, but not infectious spirochetes, can remain adjacent to cartilage for extended periods after antibiotic treatment. B. burgdorferi was not recovered by culture or xenodiagnosis with ticks after antibiotic treatment of WT mice and all but one of the immunodeficient mice with heightened pathogen burden due to impaired TLR responsiveness. Amorphous GFP+ deposits were visualized by intravital microscopy in the entheses of antibiotic-treated mice infected with GFP-expressing spirochetes and on the ear cartilage surface in sites where immunofluorescence staining detected spirochete antigens. Naive mice were not infected by tissue transplants from antibiotic-treated mice even though transplants contained spirochete DNA. Tissue homogenates from antibiotic-treated mice induced IgG reactive with B. burgdorferi antigens after immunization of naive mice and stimulated TNF-α production from macrophages in vitro. This is the first direct demonstration that inflammatory B. burgdorferi components can persist near cartilaginous tissue after treatment for Lyme disease. We propose that these deposits could contribute to the development of antibiotic-refractory Lyme arthritis.

A wire-flooring model for inducing lameness in broilers: evaluation of probiotics as a prophylactic treatment.

Bacterial chondronecrosis with osteomyelitis (BCO) is the most common cause of lameness in commercial broilers. Bacteria entering the blood via translocation from the respiratory system or gastrointestinal tract spread hematogenously to the proximal epiphyseal-physeal cartilage of rapidly growing femora and tibiae, causing BCO. We tested the hypothesis that rearing broilers on wire flooring should increase the incidence of BCO by persistently imposing additional torque and shear stress on susceptible leg joints. We also tested the hypothesis that probiotics might attenuate bacterial translocation and thereby reduce the incidence of BCO. In 5 independent experiments using 4 commercial lines, broilers grown on wire flooring developed lameness attributable predominately to BCO. The fastest-growing birds were not necessarily the most susceptible to lameness on wire flooring, nor did the genders differ in susceptibility in the 2 experiments that included both male and female broilers. The pathogenesis of BCO is not instantaneous, and accordingly, many broilers that did not exhibit lameness, nevertheless, did possess early pathognomonic lesions. These subclinical lesions were equally likely to develop in the right or left leg. The lesion status of the proximal femoral head did not determine the lesion status of the ipsilateral or contralateral proximal tibial head and vice versa. Broilers reared on wire flooring consistently had higher incidences of lameness than hatch-mates reared on wood-shavings litter. Adding probiotics to the diet beginning at 1 d of age consistently reduced the incidence of lameness for broilers reared on wire flooring. These experiments indicate that probiotics administered prophylactically may constitute an alternative to antibiotics for reducing lameness attributable to BCO. Rearing broilers on wire flooring provides an important new research model for investigating the etiology, pathogenesis, and treatment strategies for BCO.

Mycoplasma synoviae invades non-phagocytic chicken cells in vitro.

Mycoplasma synoviae and Mycoplasma gallisepticum are major poultry pathogens, but their strains differ significantly in invasiveness and pathogenicity. Recent studies have demonstrated that M. gallisepticum invades chicken erythrocytes (CER) and chicken embryonic fibroblasts. The aim of this study was to determine whether M. synoviae also invades chicken cells. Using the gentamicin invasion assay, relative invasion frequency (RIF) of four M. synoviae strains was determined for CER, chicken embryonic cell line (CEC-32) and/or primary chicken chondrocytes (CCH). All tested strains of M. synoviae were capable of invading chicken cells within 24 h after infection. The type strain WVU 1853 showed significantly higher invasiveness in CER (RIF 7.5+/-1.5%) and CEC-32 (RIF 7.0+/-0.3%) than field strain ULB 02/T6 and M. gallisepticum strain R(low). Surprisingly, WVU 1853, which is capable of causing synovitis and arthritis in chickens, was less invasive for CCH with a RIF (1.2+/-0.3%) similar to that of R(low) (1.1+/-0.1%). This is the first study documenting the invasiveness of M. synoviae strains for non-phagocytic chicken cells.

Inflammatory pseudotumoural endotracheal mucormycosis with cartilage damage.

Mucormycosis is a rare opportunistic infection usually associated with immunosuppression, diabetes mellitus or haematological malignancy. Herein, we report an unusual case of mucormycosis in a 46-yr-old male patient with diabetes presenting with an endotracheal mass obstructing the trachea and cartilage damage. Histological examination of the bronchoscopy biopsy specimens revealed invasive mucormycosis. The patient was treated with intravenous amphotericin B followed by removal of the lesion via bronchoscopy.

High hydrostatic pressure, a novel approach in orthopedic surgical oncology to disinfect bone, tendons and cartilage.

High hydrostatic pressure (HHP) is widely used in the food processing industry, for example to inactivate vegetative microorganisms in meat products, milk and juice, thereby avoiding the addition of any chemical preservatives. Besides this, HHP is also an attractive novel approach to effectively kill vegetative microorganisms or tumor cells in bone, cartilage and tendon ex vivo while leaving the tissues' mechanical properties unimpaired, thus allowing reimplantation of the resected tissue explants. In contrast, sterilization by gamma irradiation and thermal or chemical inactivation of potentially infected autografts, allografts and other biomaterials considered for tissue regeneration and reconstruction is often associated with deterioration of the mechanical, physical and biological properties of the implant. HHP technology is now in preclinical testing with the aim of disinfecting/devitalizing grafts in order to inactivate both vegetative microorganisms and tumor cells in resected bone tissue segments, eventually allowing reimplantation of resected bone segments initially afflicted with osteomyelitis or tumors. The technical advantages, state-of-the-art, and potential application of HHP in orthopedic surgery are reviewed.

Is osteoarthritis an infection-associated disease and a target for chemotherapy?

The treatment of osteoarthritis (OA) continues to be a challenge, and current treatment modalities are disappointing. New approaches in therapy may be developed as a result of evidence of the involvement of inflammatory cytokines in the progression of OA. Cotrimoxazole (sulfamethoxazole/trimethoprim) was noted to have anti-inflammatory properties and has been used in the therapy of several autoimmune diseases. Analyzing our own and world experience, we propose that OA and degenerative joint and spine disease might be infection-associated diseases and a target for sulfamethoxazole/trimethoprim therapy.

Pseudomonas aeruginosa otochondritis complicating localized cutaneous leishmaniasis: prevention of mutilation by early antibiotic therapy.

A patient with an ulcerated cutaneous leishmaniasis of the pinna had suppurative otochondritis after a first unsuccessful course of treatment with meglumine antimoniate. Although the Leishmania ulceration healed after a second course of meglumine antimoniate, and despite three oral dicloxacillin or pristinamycin courses, the otochondritis extended and an abscess developed. Pus from the abscess revealed a pure culture of Pseudomonas aeruginosa. Five days of oral ciprofloxacin plus rifampin led to a marked improvement. The P. aeruginosa isolate was sensitive to ciprofloxacin but fully resistant to rifampin. Healing with minimal mutilation was obtained at the end of a six-week course of multiple antibiotic therapy. Pseudomonas aeruginosa otochondritis was a co-factor of cartilage mutilation in this patient. Thus, infection with P. aeruginosa should be promptly treated when present in tender cutaneous or mucosal leishmaniasis lesions near cartilaginous areas.

Salvage of infected cartilage grafts for nasal reconstruction with a through-and-through irrigation system.

Development of a wound infection after nasal reconstruction can place the entire reconstructive effort in jeopardy. The approach to management in these cases has traditionally entailed wound drainage, removal of involved graft material, and debridement of nonvital tissue. Following adequate wound healing, delayed reconstruction is then performed, with the final result often compromised in form and function. We present a case of a postoperative wound infection following reconstruction of a traumatic nasal deformity utilizing autologous cartilage grafts. Treatment consisted of hospitalization with administration of culture-specific parenteral antibiotics and continuous through-and-through antibiotic irrigation of the wound via an indwelling catheter. The infection was completely eradicated and all cartilage grafts were salvaged utilizing this technique. At 3 years postoperatively, the patient has maintained the shape and quality of her reconstruction, without evidence of recurrent infection.

Metalloproteinase-7 contributes to joint destruction in Staphylococcus aureus induced arthritis.

Septic arthritis induced by Staphylococcus aureus causes a rapid destruction of joint cartilage and periarticular bone. The mechanisms behind this phenomenon are not fully understood. Earlier studies have shown that cytokines and metalloproteinases are of importance in bone metabolism. Matrix metalloproteinase-7 (MMP-7) has pleiotropic function including facilitating migration of both macrophages and neutrophils. The aim of this study has been to investigate the significance of MMP-7 expression in septic arthritis. MMP-7 deficient mice and congeneic controls were intravenously inoculated with an arthritogenic dose of S. aureus LS-1. This study shows that MMP-7 deficient mice exposed to S. aureus developed significantly less severe arthritis both clinically and histologically. Despite this finding, bacterial growth in the deficient animals was significantly increased. In vitro responses to staphylococcal antigens and superantigens did not differ between MMP-7(+/+) and MMP-7(-/-) mice with respect to cytokine production and if anything increased the production of certain chemokines. In addition MMP-7(-/-) mice exhibited decreased numbers of peripheral blood mononuclear cells before and one day after bacterial inoculation, but increased numbers of peripheral granulocytes on day 1. In conclusion, MMP-7 contributes to the development of a destructive course of septic arthritis despite decreased bacterial load. In addition, expression of MMP-7 is of importance for the distribution of peripheral leukocytes.