Osteoarthritic (OA) chondrocytes are metabolically active, displaying increased synthesis of type II collagen. Here, we show by immunohistochemistry and polymerase chain reaction that in comparison with healthy cartilage, OA articular chondrocytes exhibit increased in vivo synthesis of collagen prolyl-4-hydroxylase type II, a pivotal enzyme in collagen triple helix formation. Exposure of primary human articular chondrocytes to 1% oxygen enhanced accumulation of native type II collagen and stabilized hypoxia-inducible factor-1␣ (HIF-1␣). This effect was abolished by addition of the HIF-1 inhibitor 2-methoxyestradiol. Real-time polymerase chain reaction analyses of mRNAs from these cultures revealed increased transcript levels of both ␣-subunits of prolyl-4-hydroxylase (P4HA1, ϳ2-fold; P4HA2, ϳ2.3-fold) and of classical HIF-1 target genes (glucosetransporter-1, ϳ2.1-fold; phosphoglyceratekinase-1, ϳ2.2-fold). Treatment of hypoxic chondrocytes with 2-methoxyestradiol reduced transcriptional activity of HIF-1 and synthesis of ␣(II), and to a lesser extent ␣(I), subunits of collagen prolyl-4-hydroxylases. mRNA levels of type II collagen (Col2A1) and the ␤-subunit (P4HB) of prolyl-4-hydroxylase, however, displayed only modest changes at 1% oxygen. From these results and our in vivo data, we inferred that besides increased Articular hyaline cartilage is the most important component in synovial joints for frictionless joint motion. During movement, the articular cartilage is compressed by load and is then able to recover from this deformity. These unique biomechanical properties depend on the specific zonal architecture of articular cartilage as well as the extracellular matrix (ECM), which consists of two phases: solid and fluid phases. The main ECM components are proteoglycans, glycoproteins, and collagens, mainly type II collagen.1-3 Type II collagen is synthesized as a procollagen molecule with noncollagenous amino and carboxy extension peptides, by articular chondrocytes which represent the only living elements within hyaline cartilage. 4 Large type II collagen fibrils form a network with embedded proteoglycans, glycoproteins, water, and soluble ions. Since this collagen network is established in adults, the half-life of collagens is estimated to be over decades.Proper function of a load-bearing joint depends on the structural integrity of this highly specialized cartilage tissue and its ability to absorb and respond to mechanical stress. During the course of osteoarthritis, increased degradation processes of the ECM by mechanical factors as well as activity of metalloproteinases and aggrecanases have been observed. 5,6 Ultimately, destruction of large parts of the collagen network and ion-binding capacity via loss of negatively charged proteoglycans lead to a significantly decreased water-binding capability of the ECM. These biochemical changes are responsible for the devel-

Patients with advanced lifelimiting disease often suffer from symptoms that considerably impair their quality of life and that of their families. Palliative care aims to alleviate these symptoms by a multidimensional approach. Pharmacotherapy is an essential component. The objective of this review is to give an overview of symptomoriented drug therapy for the most important symptoms in palliative care. Leading symptoms that affect quality of life include pain, dyspnea, nausea and emesis, weakness and disorientation. Careful examination and history taking help to understand the individual mechanisms underlying these symptoms. Specific pharmacotherapy provides an efficient way to achieve symptom control in the context of palliative care.