Objective : To assess the role of matrix metalloproteinases (MMPs) in cartilage and bone erosions in Lyme arthritis Methods We examined synovial fluid from 10 patients with Lyme arthritis for the presence of MMP‐2, MMP‐3, MMP‐9, and “aggrecanase” activity using gelatinolytic zymography and immunoblot analysis. We developed an in vitro model of Lyme arthritis using cartilage explants and observed changes in cartilage degradation in the presence of Borrelia burgdorferi and/or various protease inhibitors. Results Synovial fluid from patients with Lyme arthritis was found to contain at least 3 MMPs: gelatinase A (MMP‐2), stromelysin (MMP‐3), and gelatinase B (MMP‐9). In addition, there was evidence in 2 patients of “aggrecanase” activity not accounted for by the above enzymes. Infection of cartilage explants with B burgdorferi resulted in induction of MMP‐3, MMP‐9, and “aggrecanase” activity. Increased induction of these enzymes by B burgdorferi alone was not sufficient to cause cartilage destruction in the explants as measured by glycosaminoglycan (GAG) and hydroxyproline release. However, addition of plasminogen, which can act as an MMP activator, to cultures resulted in significant GAG and hydroxyproline release in the presence of B burgdorferi. The MMP inhibitor batimastat significantly reduced the GAG release and completely inhibited the collagen degradation. Conclusion MMPs are found in synovial fluids from patients with Lyme arthritis and are induced from cartilage tissue by the presence of B burgdorferi. Inhibition of MMP activity prevents B burgdorferi–induced cartilage degradation in vitro.
Studies of the protein function of Borrelia burgdorferi have been limited by a lack of tools for manipulating borrelial DNA. We devised a system to study the function of a B. burgdorferi oligopeptide permease (Opp) orthologue by complementation with Escherichia coli Opp proteins. The Opp system of E. coli has been extensively studied and has well defined substrate specificities. The system is of interest in B. burgdorferi because analysis of its genome has revealed little identifiable machinery for synthesis or transport of amino acids and only a single intact peptide transporter operon. As such, peptide uptake may play a major role in nutrition for the organism. Substrate specificity for ABC peptide transporters in other organisms is determined by their substrate binding protein. The B. burgdorferi Opp operon differs from the E. coli Opp operon in that it has three separate substrate binding proteins, OppA-1, -2 and -3. In addition, B. burgdorferi has two OppA orthologues, OppA-4 and -5, encoded on separate plasmids. The substrate binding proteins interact with integral membrane proteins, OppB and OppC, to transport peptides into the cell. The process is driven by two ATP binding proteins, OppD and OppF. Using opp-deleted E. coli mutants, we transformed cells with B. burgdorferi oppA-1, -2, -4 or -5 and E. coli oppBCDF. All of the B. burgdorferi OppA proteins are able to complement E. coli OppBCDF to form a functional Opp transport system capable of transporting peptides for nutritional use. Although there is overlap in substrate specificities, the substrate specificities for B. burgdorferi OppAs are not identical to that of E. coli OppA. Transport of toxic peptides by B. burgdorferi grown in nutrient-rich medium parallels borrelial OppA substrate specificity in the complementation system. Use of this complementation system will pave the way for more detailed studies of B. burgdorferi peptide transport than currently available tools for manipulating borrelial DNA will allow.
Nursing home care in the USA is part of the costliest health‐care system in the world, and is a heavily regulated industry still struggling to maintain quality care across the country. The modern nursing home dates back to the 1930s and the passage of the Social Security Act, with continued growth of the industry after the 1960s, when the Medicare and Medicaid programs were created. As in other industrialized countries, the elderly population in the USA is growing, and the highest growth is occurring among those older than 85. This is the group with the highest health‐care costs and rates of nursing home utilization. There are two major types of care provided in US nursing homes: long‐term and subacute care. In the 1980s, quality of care became an important concern, which led to major reform and passage of new regulations under the law known as OBRA‐87. During this time, the Minimum Data Set (MDS), which is a comprehensive assessment tool, was introduced. It continues to be a vital tool for both payment and research. Reform also ushered in the state survey process, which scrutinizes nursing homes yearly and assesses financial penalties for substandard care. The aging of the American population will provide challenges for financing nursing home care in the future. The use of private long‐term care insurance is growing, and may be an important source of payment for this type of care in the decades to come.
Matrix metalloproteinases (MMPs) are associated with chronic neurologic diseases such as multiple sclerosis and senile dementia. Lyme disease is a multisystemic infection involving the nervous system, skin, joints, and heart. Neurologic manifestations of chronic Lyme disease include encephalopathy and cranial and peripheral neuropathy. Borrelia burgdorferi, the spirochaete causing Lyme disease, has been cultured from the cerebrospinal fluid (CSF), and B. burgdorferi DNA is frequently detected in the CSF of patients with Lyme neuroborreliosis. We used cerebral and cerebellar primary cultures to determine whether B. burgdorferi induces the production of MMPs by primary neural cultures. B. burgdorferi in a dose- and time-dependent manner induced the expression of MMP-9 by primary neural cultures but had no effect on the expression of MMP-2. Human and rat type I astrocytes expressed MMP-9 when incubated with B. burgdorferi in the same manner as primary neural cultures. This response may play a role in the symptomatology and the pathogenesis of Lyme neuroborreliosis.
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