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Articular chondrocytes of achondroplastic mice (cn/cn) resemble ultrastructurally those of their non-achondroplastic siblings (Cn/Cn or Cn/cn), except for premature deposition of glycogen and a tendency to undergo regression. The latter may be slight or extreme. The ultimate cause of the vulnerability of the chondrocytes and the cause of the heterogeneity of the reaction could not be determined with the method employed. Nevertheless, increased vulnerability accounts for cell death under conditions which are usually not injurious, and which may be either physiologic or altered by endogenous or exogenous factors.

10 days’ to 3 months’ consumption of a diet containing 4% cholesterol causes a minor and transitory stimulation of articular chondrocytes of mice. The transitory disturbance is accompanied by a more permanent increase in glycogen, by abnormal deposition of cytoplasmic lipid and by an increase in the fibrillarity of the pericellular matrix. The changes are consistent with the failure of the cholesterol diet to influence the course of osteoarthrosis if fed to mice from an early age through life.

The effect of insulin on the ultrastructure of articular chondrocytes was studied in young dwarf mice (dwdw) which lack pituitary eosinophiles and fail to produce STH. Within less than 24 hours, injections of insulin together with dextrose enhanced development of the endoplasmic reticulum and of the Golgi structures, stimulated the mitochondria, and accelerated and intensified glycogen formation. Dextrose alone had a similar, although less marked effect. The findings suggest a slightly promoting influence of insulin on protein synthesis and a conspicuous stimulation of carbohydrate synthesis by articular chondrocytes of hypopituitary dwarf mice thus treated. The results were compared with those obtained previously after treatment with somatotrophin, and the relationship between these two hormones was discussed.

The early effects of somatotrophin on the fine structure of the cartilage of the hip joint were studied in growing mice given a single injection of STH, and examined one-half, one, two, four, eight or 24 hours after injection. The first changes, observed as early as one hour after treatment with the hormone, consisted of swelling of the ground plasma and of the pericellular matrix. With increasing interval from the time of injection, acceleration and intensification of organellar development associated with hypertrophy of the cytoplasm were noted: There was increase in the number of RNA granules, of ER lamellae, of multivesicular bodies and of mitochondria as well as hypertrophy of the Golgi apparatus. The mitochondria were swollen, vacuolated or distorted. The appearance of glycogen was hastened. The changes were most marked in superficial and upper midzonal cells, and were still conspicuous 24 hours after the injection. The response of the Golgi apparatus was retarded as compared to that of other organelles. The significance of the findings in relation to cell function is discussed.

Articular chondrocytes of 1-year-old male mice of strain C57B1 were stimulated by injections of a cartilage-bone marrow extract to undergo hypertrophy, intensified organellar development and hyperplasia. This response was attenuated as compared with that of growing animals treated similarly. The morphological findings are consistent with some increase in synthetic activity on the part of the chondrocytes. The increased cell death observed was attributed to overstimulation and subsequent exhaustion, and was considered responsible for the prominence of microscars in the matrix.

Long spacing bodies with a characteristic pattern of striation were found in the articular cartilage of the femoral head of 1-year-old mice of strain C 57 B1. The structures were compared with similar ones found in tissues other than cartilage, and potential etiologic factors were discussed.

Young adult male mice of strain Cδ7Bl were treated with somatotrophin, thyroxine or estradiol benzoate and were observed for 24 h, 2, 4 days or 1 or 2 weeks. The articular cartilage of the femoral head reacted to the treatment with ultra-structural changes in cells and matrix. Chondrocytes were relatively less and the matrix was relatively more conspicuously altered than in growing mice treated similarly. The changes observed are consistent with accelerated passage of cell products into the matrix and with altered cellular activity in regard to the production of components of the matrix. Early effects were followed by intensified degeneration and death of chondrocytes.

Transverse frozen sections of desheathed rat peripheral nerve were incubated in media of different composition prior to fixation and processing for electron microscopic examination. Neurofilaments remained intact when these tissues were incubated in calcium-free media. A loss of neurofilaments and their replacement by granular debris occurred in myelinated and unmyelinated fibers following incubation in media containing 2 mM calcium. The calcium-mediated disruption of neurofilaments was inhibited by preincubation or incubation with 1 mM p-chloromercuribenzoate (PCMB). The inhibition by preincubation with PCMB could be partially reversed by subsequent preincubation with 10 mM dithioerythritol (DTE). Calcium-mediated breakdown of neurofilaments did not occur after prolonged preincubation in calcium-free media, a finding which suggested that neurofilament disruption was dependent upon a tissue which could be lost or inactivated in frozen-sectioned nerve tissues. The findings of the present study provide morphological evidence that neurofilament disruption in mammalian peripheral nerve is mediated by a calcium-activated, PCMB-sensitive enzyme in the axoplasm of myelinated and unmyelinated nerve fibers.

The sequence of changes in transected rat sciatic nerves were subjected to parallel ultrastructural and biochemical studies. Widespread granular disintegration of axoplasmic microtubules and neurofilaments occurred in the 24--72 hour interval following nerve transection. These changes were associated with a loss of neurofilament proteins and a marked enhancement of 53,000, 70--73,000 and 85,000 MW proteins in transected nerve. The emergence of prominent nerve proteins during the aftermath of axonal degeneration supports their derivation from axonal sources. These three proteins remained prominent components in transected nerves and comprised the major proteins found in 34-day transected nerves. Amorphous granular breakdown products from myelinated and unmyelinated nerve fibers were encountered with progressively decreasing frequency after 48 hours. This diminution of intracellular axonal debris was accompanied by the appearance and increasing prominence of amorphous granular deposits within the endoneurium of transected nerves. These endoneurial deposits became closely associated with collagen fibers and persisted as a prominent component in 34-, 80- and 120-day transected nerves. It is suggested that the amorphous endoneurial granular deposits arise in part from the externalization of granular axoplasmic breakdown products. Externalized axonal components could have important implications for tissue reaction to injury.

Weanling male mice of strain C57B1. were fed a lard-enriched diet for periods of 1, 4, 7, 10, 14, or 28 days. Beginning during the second week of consumption of this ration, articular chondrocytes of the femoral heads were increased in number and size and showed ultrastructural changes. The latter manifested themselves in nuclear enlargement, intensification of organellar development and in acceleration of regression. There was no evidence of abnormal deposition of lipid material within the chondrocytes beyond that due to organellar disintegration. It was concluded that the early effects of a lard-enriched diet on articular cartilage consist of an overall stimulation of cell function followed by premature exhaustion. The primary site of action of the dietary fat remains unknown.

Administration of somatotropic hormone to newborn or weanling mice of strain C57BL Jax6 for one, two, or four weeks accelerated articular growth and development. The organelles were increased in number and the appearance of granular endoplasmic reticulum, Golgi vacuoles, multivesicular bodies, and glycogen was hastened. Toward the end of the developmental cycle, the chondrocytes swelled excessively and their plasmalemma ruptured without evidence of vascular erosion. After four weeks of treatment, there was premature breakdown of chondrocytes, their place being taken by fibrillar microscars. In the matrix, development of fibers was accentuated. The intensification of fibrillarity was followed by disorientation of the superficial collagen fibers with fraying of the articular covering. The functional significance of these findings, as well as their relation to aging changes in cartilage, is discussed.