Subchondral Bone Plate Sclerosis during Late Osteoarthritis is Mediated by Loading- induced Decrease in Sclerostin Amount X. Ma, H. Jia, W. Tong, Z. Yang,

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Subchondral Bone Plate Sclerosis during Late Osteoarthritis is Mediated by Loading- induced Decrease in Sclerostin Amount X. Ma, H. Jia, W. Tong, Z. Yang, Z. Sun, A. Chandra, L. Han, K. Zhang, J.-C. Wang, M. Enomoto-Iwamoto, L. Qin Osteoarthritis and Cartilage Volume 25, Pages S296-S297 (April 2017) DOI: 10.1016/j.joca.2017.02.500 Copyright © 2017 Terms and Conditions

Fig. 1. Egfr CKO mice develop local SBP sclerosis underneath the severely damaged cartilage area after OA surgery. (A) Safranin O staining of WT, Wa5, and CKO mouse sham and DMM joints at medial site 2 months post surgery. Dashed lines depict SBP. (B) μCT images of femoral epiphyseal region. M: medial site; L: lateral site. Red arrows point to thickened SBP at the medial site of CKO joint after DMM. (C) IHC of osteocalcin to identify osteoblasts (red arrowheads) beneath SBP in DMM joints. (D) IHC of Sclerostin in SBP in DMM joints. Green arrows point to reduced Sclerostin staining at medial site of CKO DMM knees. n=4–10/genotype. Osteoarthritis and Cartilage 2017 25, S296-S297DOI: (10.1016/j.joca.2017.02.500) Copyright © 2017 Terms and Conditions

Fig. 2. SBP sclerosis in aging Egfr CKO knees are caused by increased bone formation along SBP surface and suppressed Sclerostin expression in SBP. (A) Safranin O staining of femoral epiphyseal region in 12-month-old WT, Wa5, and CKO mice. Dashed lines: SBP. (B) μCT images of femoral epiphyseal region. Red arrows point to thickened SBP in CKO joints. (C) IHC of osteocalcin to identify osteoblasts (red arrowheads) beneath SBP. (D) IHC of Sclerostin in SBP. n=4/genotype. Osteoarthritis and Cartilage 2017 25, S296-S297DOI: (10.1016/j.joca.2017.02.500) Copyright © 2017 Terms and Conditions

Fig. 3. Late OA symptoms after DMMH include thickened SBP and its associated reduction in osteocytic sclerostin amount. H&E staining (A,D) showed obvious SBP thickening (depicted by red lines) at the medial site (M) only. Sclerostin staining (B,C,E,F) on neighboring sections revealed reduced staining in medial site of DMMH knees (E). Black squares in A and D depict the corresponding areas for B,C,E,F. n=3 mice. Osteoarthritis and Cartilage 2017 25, S296-S297DOI: (10.1016/j.joca.2017.02.500) Copyright © 2017 Terms and Conditions