OBJECTIVE: Sclerostin plays a major role in regulating skeletal bone mass, but 
its effects in articular cartilage are not known. The purpose of this study was 
to determine whether genetic loss or pharmacologic inhibition of sclerostin has 
an impact on knee joint articular cartilage.
METHODS: Expression of sclerostin was determined in articular cartilage and bone 
tissue obtained from mice, rats, and human subjects, including patients with 
knee osteoarthritis (OA). Mice with genetic knockout (KO) of sclerostin and 
pharmacologic inhibition of sclerostin with a sclerostin-neutralizing monoclonal 
antibody (Scl-Ab) in aged male rats and ovariectomized (OVX) female rats were 
used to study the effects of sclerostin on pathologic processes in the knee 
joint. The rat medial meniscus tear (MMT) model of OA was used to investigate 
the pharmacologic efficacy of systemic Scl-Ab or intraarticular (IA) delivery of 
a sclerostin antibody-Fab (Scl-Fab) fragment.
RESULTS: Sclerostin expression was detected in rodent and human articular 
chondrocytes. No difference was observed in the magnitude or distribution of 
sclerostin expression between normal and OA cartilage or bone. Sclerostin-KO 
mice showed no difference in histopathologic features of the knee joint compared 
to age-matched wild-type mice. Pharmacologic treatment of intact aged male rats 
or OVX female rats with Scl-Ab had no effect on morphologic characteristics of 
the articular cartilage. In the rat MMT model, pharmacologic treatment of 
animals with either systemic Scl-Ab or IA injection of Scl-Fab had no effect on 
lesion development or severity.
CONCLUSION: Genetic absence of sclerostin does not alter the normal development 
of age-dependent OA in mice, and pharmacologic inhibition of sclerostin with 
Scl-Ab has no impact on articular cartilage remodeling in rats with 
posttraumatic OA.