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Updated: Aug 18, 2026
Software-Assisted Quantitative Measurement of Osteoarthritic Subchondral Bone Thickness
Published on: March 18, 2022
Degenerative knee joint disease in mice lacking 3'-phosphoadenosine 5'-phosphosulfate synthetase 2 (Papss2) activity:
Alice F Ford-Hutchinson1, Zenobia Ali, Ruth A Seerattan
1Department of Biochemistry and Molecular Biology, The McCaig Center for Joint Injury and Arthritis Research, University of Calgary, Calgary, Alberta, T2N 4N1, Canada.
Objective:
Murine brachymorphism (bm) results from an autosomal recessive mutation of the Papss2 gene that encodes 3'-phosphoadenosine 5'-phosphosulfate synthetase 2, one of the principal enzymes required for the sulfation of extracellular matrix molecules in cartilage and other tissues. A spondyloepimetaphyseal dysplasia has been identified in Pakistani kindred having a mutation of PAPSS2. In addition to skeletal malformations that include short stature evident at birth due to limb shortening, brachydactyly, and kyphoscoliosis, affected individuals demonstrate premature onset degenerative joint disease. We investigated whether loss of Papss2 activity would similarly lead to degenerative joint disease in mice.
Methods:
Mice carrying the bm mutation on a C57BL/6 background were obtained from the Jackson Laboratory. Limbs were analyzed by micro-computed tomography (microCT) and histology.
Results:
At 12 months of age both male and female bm mice exhibited severe degenerative knee joint disease, with cartilage damage being primarily evident in the patello-femoral and medial compartments. Control 12-14-month-old C57BL/6 mice, in contrast, only occasionally demonstrated minimal cartilage damage. muCT imaging of bm limbs revealed shortened diaphyses associated with flared metaphyses in the proximal elements of both fore and hind limbs. Additionally, the bm hind limbs demonstrated extensive structural alterations, characterized by distortion of the patello-femoral groove, and prominent bowing of both tibia and fibula.
Conclusions:
The bm mutant, which develops severe articular cartilage lesions of the knee joint by approximately 12 months of age, represents a novel example of murine degenerative joint disease, possibly representing a model of human PAPSS2 deficiency-associated arthrosis.
Insights
Murine brachymorphism (bm) mice with a Papss2 gene mutation develop severe knee joint disease by 12 months. This finding suggests a potential model for human PAPSS2 deficiency-associated arthrosis.
Area of Science:
- Genetics and Molecular Biology
- Skeletal Biology
- Biochemistry
Background:
- Murine brachymorphism (bm) is caused by a mutation in the Papss2 gene, essential for extracellular matrix sulfation.
- PAPSS2 mutations in humans are linked to spondyloepimetaphyseal dysplasia and premature degenerative joint disease.
- The study investigates if loss of Papss2 activity in mice leads to similar joint degeneration.
Purpose of the Study:
- To determine if loss of Papss2 activity in mice results in degenerative joint disease.
- To characterize the skeletal and joint phenotypes of bm mice.
Main Methods:
- Utilized mice with the bm mutation on a C57BL/6 background.
- Analyzed limb structure using micro-computed tomography (microCT).
- Performed histological examination of joint tissues.
Main Results:
- bm mice at 12 months exhibited severe degenerative knee joint disease, particularly in the patello-femoral and medial compartments.
- microCT revealed shortened diaphyses and flared metaphyses in bm limb bones.
- Hind limbs of bm mice showed significant structural alterations, including patello-femoral groove distortion and bowing of tibia and fibula.
Conclusions:
- The bm mutant mouse develops severe articular cartilage lesions, serving as a model for murine degenerative joint disease.
- This model may represent human PAPSS2 deficiency-associated arthrosis.
- Further research can explore therapeutic strategies for PAPSS2-related joint conditions.
