Skip to main content


Delineating biologic pathways involved in skeletal growth and homeostasis through the study of rare Mendelian diseases that affect bones and joints

We have found that the secreted glycoprotein, lubricin, is mutated in patients with the autosomal recessive disorder camptodactyly–arthropathy–coxa vara–pericarditis syndrome. To better define lubricin's role in articulating joints we have been studying lubricin knockout mice. Knockout mice recapitulate features observed in patients with camptodactyly–arthropathy–coxa vara–pericarditis, and therefore allow us to learn more about the protein's in vivo function. We find that synoviocytes from knockout mice have different growth characteristics than do wild-type synoviocytes. We also find that the articular cartilage surface in knockout mice loses superficial zone chondrocytes and becomes covered by proteinaceous material. These results indicate that lubricin protects cartilage surfaces and helps regulate synovial cell growth.

We had found that Wnt-inducible-secreted protein 3 (WISP3) is mutated in patients with the autosomal recessive disorder progressive pseudorheumatoid dysplasia. Patients with progressive pseudo-rheumatoid dysplasia require joint replacement surgery for what resembles end-stage osteoarthritis by their second decade of life. WISP3 is in very low abundance since we have only been able to detect mRNA by reverse transcription-polymerase chain reaction, and not by northern blot or in situ hybridization. Furthermore, we have not been able to detect endogenous WISP3 protein using a sensitive polyclonal antibody. Therefore, to determine the role of WISP3 in maintaining joints we created Wisp3 knockout mice. Surprisingly these mice did not develop joint failure, but they did seem to have altered timing of their secondary centers of ossification. We are currently exploring whether this altered timing is relevant to the pathogenesis of cartilage failure in human patients.

We have been searching for the gene responsible for autosomal recessive acromesomelic dysplasia. This is an interesting disorder because it primarily affects postnatal, rather than prenatal, growth. Also interesting is the fact that many carrier parents of affected individuals appear to have isolated short stature. Consequently, the discovery of the gene responsible for this disease may provide insights into pathways that effect growth.

Author information

Rights and permissions

Reprints and Permissions

About this article


  • Knockout Mouse
  • Arthropathy
  • Pericarditis
  • Autosomal Recessive Disorder
  • Cartilage Surface