Biochemical Studies of Human Cartilage During the Aging Process*

Abstract

The major changes associated with the degeneration of human joints occur in the articular cartilage. However, the distinction between the degenerative process and the normal aging process has not been made definitively. Recent articles have emphasized the histologic aspects of the degenerative changes, but these same changes have not been studied histochemically. There have been some biochemical studies on human costal cartilage, but this cartilage was obtained at autopsy. Iob and Swanson (1) in 1937, working with fetal epiphyseal and costal cartilage, determined the extracellular and intracellular water by means of electrolyte studies. Their material was obtained at autopsy, eight to sixteen hours after death. Hagerty et al.(2) in 1960, using human costal cartilage from "fresh cadavers," carried out histologic examinations and studies of metabolism and water and electrolyte exchanges. Our present study is an attempt to record the histochemical changes which occur within normal human cartilage as a result of aging.Acquisition of normal human articular cartilage proved to be difficult. Tissue obtained at autopsy could not be used because of the electrolyte shifts that take place during and following death. We therefore found it necessary to use cartilage from surgical specimens. However, if the surgical operation was being performed for disease or degeneration of the joint, the cartilage of that joint could not be regarded as normal. It was necessary to rely upon cartilage removed from joints not affected by disease or degeneration. Our major source of cartilage was from amputation specimens. For example, if the amputation had been performed to remove a malignant lesion involving the proximal femur, then the articular surfaces of the knee and foot might be normal. However, even in these instances, 1 2 J. S. MILES AND L. EICHELBERGERVol. X I I if the patient had experienced prolonged disability as a result of sarcoma, the cartilage would show evidence of atrophy and could not be considered normal.Other abnormalities also necessitated the discarding of specimens, e.g., significant degenerative arthritis or disease demonstrated roentgenographically, microscopically, or on gross examination. Thus many factors were considered before the cartilage specimen was accepted. These decisions had to be made with uniformit'y, and therefore were made each time by JSM, although the specimens were obtained from the clinics at both the University of Colorado and the University of Chicago.The cartilage accepted for this study was handled in a manner identical with that described in previous papers (3-5). In most instances the amount of material from a single joint was sufficient for the analyses. There was no combining of cartilage from different joints, except from those of the foot; in the foot, the amount of cartilage provided by one intertarsal joint was so small that all the material obtained from these joints was combined for analyses. The dry samples were ground to a fine powder as previously described (6).The analyses of the...

Toll‐like receptors and chondrocytes: The lipopolysaccharide‐induced decrease in cartilage matrix synthesis is dependent on the presence of toll‐like receptor 4 and antagonized by bone morphogenetic protein 7

“…Interestingly, TLR-7 was only demonstrable in chondrocytes derived from patients younger than age 35 years, suggesting that a patient's age may influence TLR expression, which is consistent with previous observations of the effects of aging in cartilage biology, particularly with regard to matrix synthesis and cell numbers, each of which shows a dramatic decrease in patients around age 30 years (24,(46)(47)(48)(49)(50). However, in our culture settings, the presence of TLRs 1-6 as well as TLR-8 and TLR-9 in human articular chondrocytes was independent of age.…”

Biochemical Findings in Normal and Osteoarthritic Articular Cartilage. II. Chondroitin Sulfate Concentration and Chain Length, Water, and Ash Content*

“…The age ranges studied are limited to older adults; no statements can be made comparing children or young adults, but the age range observed includes the period of most frequent development and progression of osteoarthritis. Other studies of articular cartilage have revealed an absence of age dependent changes in the concentration of hexosamine (17), total solids, percentage of extracellular and intracellular solids, total sulfate, and total potassium (18), although an increase in intracellular water with a decrease in extracellular water was found in older age groups (18). The failure to find significant biochemical changes in aged but normal articular cartilage and the focal distribution of the biochemical as well as pathological changes in this disease point to the need for studies of focal factors influencing metabolic phenomena in articular cartilage in analyzing the pathogenesis of osteoarthritis.…”

Pathogenesis of Degenerative Joint Disease in the Human Temporomandibular Joint

“…Collagens account for approximately 50% of the dry weight of adult articular cartilages (Miles and Eichelberger, 1964). The articular fibrocartilages of the temporomandibular joint are composed principally of type I collagen.…”

“…2 and 7). Age-related changes in the temporomandibular joint include: (i) decreased water content (Miles and Eichelberger, 1964;Bollet and Nance, 1966;Mankin and Thrasher, 1975;Grushko et al, 1989;Peyron and Altman, 1992), (ii) decreased cellular proliferation (Hammerman, 1993), (iii) accumulation of senescing cells (Dreesen and Halata, 1990;Hammerman, 1993), (iv) altered, decreased, or lost response to growth factors (Hammerman, 1993), (v) accumulation of altered proteins (Brown and Jones, 1990;Chevalier et al, 1992;Hammerman, 1993), and (vi) decreased catabolic activity (Bollet, 1969). There are also age-related changes that appear to be specific to cartilage, including: (i) decreased cellular density in the prechondroblastic region (Livne et al, 1985), (ii) accumulation of degenerating chondrocytes (Dreesen and Halata, 1990), (iii) reduction in the number and size of proteoglycans (Vasan, 1980;Lash and Vasan, 1983, and references therein), (iv) reduction in the molecular weight of the proteoglycan core protein (Hamerman, 1993), and (v) changes in the size and composition of the glycosaminoglycans (Hjertquist and Lemperg, 1972;Elliott and Gardner, 1979;Roughley and White, 1980;Lash and Vasan, 1983;Mankin, 1984;Hamerman, 1989;Ratcliffe et al, 1993).…”