EU_Musc_Nimni.qxp 24/4/08 10:24 Page 88
Cartilage
injury and an attempt of the chondrocytes to compensate for the repair. BMP-2 and BMP-7 can promote cartilage repair in various
catabolic effects of both cytokine-induced and mechanically induced models of focal cartilage defects.
11,23
BMP-2 and BMP-7 (osteogenic
injury. The BMP-2-induced elevated degradational activity is most likely protein-1/OP-1) are currently approved for multiple indications in bone
an attempt to clear away old matrix molecules to make room for the fracture repair and spinal fusion. Consistent with their roles in vivo in
newly synthesised molecules, indicating another role for BMP-2 in promoting endochondral ossification, BMPs may promote chondrocyte
cartilage remodelling.
12
hypertrophy in repair models.
Cartilage Extracellular Matrices Recently, BMP-2 was used for treating experimental OA facet joint models
The uniqueness of the structure, function and environment in which in rats. The facet joint (zygapophysial joint) is a synovial joint covered by
cartilage is located makes other factors, beyond the classic extracellular hyaline cartilage, and is enclosed by the synovium and the joint capsule.
24,25
matrix, quite relevant. The exposure of cartilage to synovial fluid and lining In degenerative lumbar spinal disorders, degeneration of the facet joint is
and of its surface to the joint space creates a unique environment for one of the causes of lower-back pain. Facet joints are clinically important
cartilage. As an example, an articular cartilage superficial zone protein (SZP) sources of chronic pain, even after spinal fusion or artificial intervertebral disc
appears to play an important cytoprotective role by preventing cellular implantation.
26,27
For the assessment of the osteoarthritic lesions of the
adhesion to the articular cartilage surface. This unique substance, also lumbar facet joint, Yeh et al.
28
developed an animal model by injection of
known as lubricin, is a mucous glycoprotein, originally identified in synovial collagenase into the rat facet joint to develop OA-like changes, and the
fluid many years ago. Some of the principal functions, such as boundary short-term therapeutic effects of rhBMP-2 on the osteoarthritic facet joint
lubrication and tissue protection, are directly related to its abilities to absorb were tested.
29
Treatment with BMP-2 effectively alleviated the OA-like
and to coat cartilage. Modifications to the structure of SZP, coupled with changes in the facet joint during the six-week period of observation. Either
inhibition of SZP synthesis during inflammation, may account for the 10 or 100mg of BMP-2 treatment can reduce the progression of OA, but the
attachment and invasion of pannus observed in inflammatory joint injection of the high-dose BMP-2 caused adverse side effects (obliteration of
disease.
21
Studies on cartilage explants as well as of monolayers of joint space) in some rats at three weeks.
chondrocytes showed that accumulation of SZP was significantly increased
by fibroblast growth factor (FGF), insulin-like growth factor (IGF), platelet- The studies described above strongly suggest that BMP-2, and possibly
derived growth factor (PDGF) and TGF-β, and reduced by IL-1 and TNF-α.
22
other members of the TGF-β family of growth factors, alone or in
Inhibition was partially reversed by BMP-7, clearly illustrating how the combination, delivered locally at sites of joint damage have the potential
interplay between cytokines and growth factors can influence the ability of to inhibit, reduce and possibly even reverse the events associated with
cartilage to maintain its functional integrity. cartilage loss. These results also emphasise the observations that dosage,
as well as timing of administration, may be critical. In particular, a high
Therapeutic Effect of Bone Morphogenetic dose of BMP can cause adverse effects that over-ride any of the potential
Proteins on Osteoarthritis benefits. As with other applications of these growth factors in general,
The capacity of several BMPs to stimulate the synthesis of the cartilage and in skeletal repair in particular, the form and mode of delivery,
matrix constituents, type II collagen and aggrecan by adult articular including carriers, have the potential to significantly affect the outcome
chondrocytes provides the basis for their use to promote cartilage of these procedures. ■
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88 EUROPEAN MUSCULOSKELETAL REVIEW
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