Differential effects of nicotine and tobacco smoke condensate on human annulus fibrosus cell metabolism.

Ferguson Laboratory for Orthopaedic Research, Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA.
Journal of Orthopaedic Research (Impact Factor: 2.88). 03/2011; 29(10):1585-91. DOI: 10.1002/jor.21417
Source: PubMed

ABSTRACT Tobacco smoking increases the risk of intervertebral disc degeneration (IDD) and back pain, but the mechanisms underlying the adverse effects of smoking are largely unknown. Current hypotheses predict that smoking contributes to IDD indirectly through nicotine-mediated vasoconstriction which limits the exchange of nutrients between the discs and their surroundings. We alternatively hypothesize that direct contact of disc cells, that is, cells in the outermost annulus and those present along fissures in degenerating discs, with the vascular system containing soluble tobacco smoking constituents could perturb normal metabolic activities resulting in IDD. In this study, we tested our hypothesis by comparing the effects of direct exposure of human disc cells to tobacco smoke condensate and nicotine on cell viability and metabolic activity. We showed that smoke condensate, which contains all of the water-soluble compounds inhaled by smokers, exerts greater detrimental effects on human disc cell viability and metabolism than nicotine. Smoke condensate greatly induced an inflammatory response and gene expression of metalloproteinases while reduced active matrix synthesis and expression of matrix structural genes. Therefore, we have demonstrated that disc cell exposure to the constituents of tobacco smoke has negative consequences which have the potential to alter disc matrix homeostasis.

  • [Show abstract] [Hide abstract]
    ABSTRACT: OBJECTIVES: The purpose of the present study was to simultaneously examine the transcript levels of a large number of MMPs (-3, -8, -9, -13 and -14) and ADAMTS-4 and to investigate their correlation with the clinicopathological profile of patients suffering from tuberculous intervertebral discs. DESIGN AND METHODS: Clinical data were collected from 130 patients participating in the study from March 2011 to April 2012. mRNA expression levels were determined by means of the real-time polymerase chain reaction in 60 tuberculous (TB), 60 herniated, and 10 control intervertebral disc (ID) specimens. RESULTS: MMP-8, -9, -13, and -14 that showed a stronger expression in spinal TB disc tissue compared to normal ID tissue (P<0.05). Our results showed multiple positive correlations among MMP-8, -9, and -13 mRNA in TB samples. Smoking habits were found to significantly up-regulate the transcript levels of MMP-3 and -13 (P<0.05). Pain intensity, duration of symptoms, CRP, and ESR significantly affected the transcript levels of several MMPs (P<0.05). CONCLUSIONS: The MMPs may drive extracellular matrix destruction in spinal tuberculosis intervertebral discs. The experimental data imply a synergistic effect on the activity of these MMPs in spinal tuberculosis intervertebral discs. Furthermore, the experimental data suggest that smoking plays an unfavourable role in the prognosis of spinal tuberculosis intervertebral discs. Moreover, pain intensity, duration of symptoms, CRP, and ESR may affect the process of extracellular matrix destruction by increasing the expression of MMPs in spinal tuberculosis intervertebral disc samples.
    Clinical biochemistry 02/2013; · 2.02 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Cigarette smoking has deleterious effects on the musculo-skeletal system. The loss of bone mineral content and increased incidence of fractures are the best known negative consequences. The pathogenesis is complex, due to direct toxic effects on osteoblasts/osteoclasts activity of nicotine, and indirect actions on sex and adrenocortical hormones, vitamin D, intestinal calcium absorption, vessels and oxygen supply. Smoking may favour the onset or aggravate the progression of rheumatoid arthritis and back pain. Negative influences have been observed on muscle and on tendons. Moreover, smoking habit is associated to a number of short term post-operative complications and higher resource consumption. Smoking cessation is highly advisable with positive effects on the bone metabolism on the long term. More positive and immediate results can be obtained in patients submitted to orthopedic surgery: the healing process is improved, the frequency of complications is reduced, and the length of hospital stay is shortened.
    Muscles, ligaments and tendons journal. 04/2013; 3(2):63-9.
  • [Show abstract] [Hide abstract]
    ABSTRACT: The intervertebral disk (IVD) is a fascinating and resilient tissue compartment given the myriad of functions that it performs as well as its unique anatomy. The IVD must tolerate immense loads, protect the spinal cord, and contribute considerable flexibility and strength to the spinal column. In addition, as a consequence of its anatomical and physiological configuration, a unique characteristic of the IVD is that it also provides a barrier to metastatic disease. However, when injured and/or the subject of significant degenerative change, the IVD can be the source of substantial pain and disability. Considerable efforts have been made over the past several decades with respect to regenerating or at least modulating degenerative changes affecting the IVD through the use of many biological agents such as growth factors, hydrogels, and the use of plant sterols and even spices common to Ayurvedic medicine. More recently stem/progenitor and autologous chondrocytes have been used mostly in animal models of disk disease but also a few trials involving humans. At the end of the day if biological therapies are to offer benefit to the patient, the outcomes must be improved function and/or less pain and also must be improvements upon measures that are already in clinical practice. Here some of the challenges posed by the degenerative IVD and a summary of some of the regenerative attempts both in vitro and in vivo are discussed within the context of the vital question: "Who is the patient?"
    Global spine journal. 06/2013; 3(3):193-200.