title: Treatment with recombinant lubricin attenuates osteoarthritis by positive feedback loop between articular cartilage and subchondral bone in ovariectomized rats.
abstract: Osteoarthritis (OA) is a most commonly multifactorial degenerative joint disease along with the aging population, particularly in postmenopausal women. During the onset of OA, articular cartilage and subchondral bone act in concert as a functional unit. This present study is to investigate the effects of early or late treatment with recombinant lubricin on the onset of osteoarthritis (OA) in ovariectomized (OVX) rats. We found that both early and late recombinant lubricin treatments attenuated the onset of OA by positive feedback loop between articular cartilage and subchondral bone, although late treatment contributed to a lesser effect compared with early treatment. Specifically, treatment with recombinant lubricin protected articular cartilage from degeneration, demonstrated by lower proteoglycan loss, lower OARSI scores, less calcification cartilage zone and reduced immunostaining for collagen X (Col X) and matrix metalloproteinase (MMP-13) but increased the expression of lubricin, in comparison with vehicle-treated OVX rat group. Further, chondroprotective effects of lubricin normalized bone remodeling in subchondral bone underneath. It's suggested that treatment with recombinant lubricin inhibited the elevation of TRAP and Osterix positive cells in OVX rats and led to the normalization of subchondral bone microarchitectures with the suppression of subsidence of bone volume ratio (BV/TV) and trabecular thickness (Tb.Th) and the increase of trabecular separation (Tb.Sp) in vehicle-treated OVX rats. What's more, the normalization of subchondral bone in turn attenuated the articular cartilage erosion by inhibiting vascular invasion from subchondral bone to calcified cartilage zone, exemplified by inhibiting the elevation of CD31 positive cells in calcified cartilage and angiography in subchondral bone. Together, these results shed light that both early and late recombinant lubricin treatments attenuate the onset of OA by balancing the interplay between articular cartilage and subchondral bone in OVX rats, while also providing a further rationale for its therapeutic targeting to postmenopausal OA and suggesting that treatment timing is a pivotal factor for better effect acquisition.
authors.affiliation: Orthopedics and Traumatology, NanFang hospital, Southern Medical University, No. 1838 Guangzhou Da Dao Bei, Guangzhou, Guangdong Province 510515, China. Electronic address: cuizhuang3816@163.com.
authors.forename: Zhuang
authors.initials: Z
authors.lastname: Cui
authors.affiliation: Orthopedics and Traumatology, NanFang hospital, Southern Medical University, No. 1838 Guangzhou Da Dao Bei, Guangzhou, Guangdong Province 510515, China. Electronic address: buzaiyouyu5945@163.com.
authors.forename: Changpeng
authors.initials: C
authors.lastname: Xu
authors.affiliation: Orthopedics and Traumatology, NanFang hospital, Southern Medical University, No. 1838 Guangzhou Da Dao Bei, Guangzhou, Guangdong Province 510515, China. Electronic address: 332478744@qq.com.
authors.forename: Xue
authors.initials: X
authors.lastname: Li
authors.affiliation: Orthopedics and Traumatology, NanFang hospital, Southern Medical University, No. 1838 Guangzhou Da Dao Bei, Guangzhou, Guangdong Province 510515, China. Electronic address: 360589376@qq.com.
authors.forename: Jinqi
authors.initials: J
authors.lastname: Song
authors.affiliation: Orthopedics and Traumatology, NanFang hospital, Southern Medical University, No. 1838 Guangzhou Da Dao Bei, Guangzhou, Guangdong Province 510515, China. Electronic address: cuizhuang5945@gmail.com.
authors.forename: Bin
authors.initials: B
authors.lastname: Yu
mesh_terms: D000135:Acid Phosphatase / Q000378:metabolism; D019386:Alendronate / Q000494:pharmacology; D000818:Animals; D002358:Cartilage, Articular / Q000187:drug effects / Q000201:enzymology / Q000473:pathology*; D024042:Collagen Type I / Q000652:urine; D024121:Collagen Type X / Q000378:metabolism; D025461:Feedback, Physiological; D005260:Female; D006023:Glycoproteins / Q000627:therapeutic use*; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism; D010003:Osteoarthritis / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology / Q000652:urine; D010052:Ovariectomy; D010455:Peptides / Q000652:urine; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D020011:Protective Agents / Q000494:pharmacology / Q000627:therapeutic use; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use*; D000071681:Tartrate-Resistant Acid Phosphatase; D013977:Tibia / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology*; D014157:Transcription Factors / Q000378:metabolism; D055114:X-Ray Microtomography; D000099158:Proteoglycan 4
chemical_list: D000135:Acid Phosphatase; D019386:Alendronate; D024042:Collagen Type I; D024121:Collagen Type X; D006023:Glycoproteins; D007527:Isoenzymes; D053509:Matrix Metalloproteinase 13; D010455:Peptides; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D020011:Protective Agents; D011994:Recombinant Proteins; D000071681:Tartrate-Resistant Acid Phosphatase; D014157:Transcription Factors; D000099158:Proteoglycan 4; C495181:Sp7 protein, rat; C052929:collagen type I trimeric cross-linked peptide
keywords: Cartilage; Lubricin; Osteoarthritis; Osteoporosis; Ovariectomy; Subchondral bone