title: Hormonal modulation of connective tissue homeostasis and sex differences in risk for osteoarthritis of the knee.
abstract: Young female athletes experience a higher incidence of ligament injuries than their male counterparts, females experience a higher incidence of joint hypermobility syndrome (a risk factor for osteoarthritis development), and post-menopausal females experience a higher prevalence of osteoarthritis than age-matched males. These observations indicate that fluctuating sex hormone levels in young females and loss of ovarian sex hormone production due to menopause likely contribute to observed sex differences in knee joint function and risk for loss of function. In studies of osteoarthritis, however, there is a general lack of appreciation for the heterogeneity of hormonal control in both women and men. Progress in this field is limited by the relatively few preclinical osteoarthritis models, and that most of the work with established models uses only male animals. To elucidate sex differences in osteoarthritis, it is important to examine sex hormone mechanisms in cells from knee tissues and the sexual dimorphism in the role of inflammation at the cell, tissue, and organ levels. There is a need to determine if the risk for loss of knee function and integrity in females is restricted to only the knee or if sex-specific changes in other tissues play a role. This paper discusses these gaps in knowledge and suggests remedies.
authors: Isis Research Network on Musculoskeletal Health, Society for Women's Health Research, 1025 Connecticut Avenue, NW Suite 601, Washington, DC, 20036, USA.|Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, 315 Ferst Drive NW, Atlanta, GA 30332-0363, USA.
authors: Barbara D
authors: BD
authors: Boyan
authors: Isis Research Network on Musculoskeletal Health, Society for Women's Health Research, 1025 Connecticut Avenue, NW Suite 601, Washington, DC, 20036, USA.
authors: David A
authors: DA
authors: Hart
authors: Isis Research Network on Musculoskeletal Health, Society for Women's Health Research, 1025 Connecticut Avenue, NW Suite 601, Washington, DC, 20036, USA.
authors: Roger M
authors: RM
authors: Enoka
authors: Isis Research Network on Musculoskeletal Health, Society for Women's Health Research, 1025 Connecticut Avenue, NW Suite 601, Washington, DC, 20036, USA.
authors: Daniel P
authors: DP
authors: Nicolella
authors: Isis Research Network on Musculoskeletal Health, Society for Women's Health Research, 1025 Connecticut Avenue, NW Suite 601, Washington, DC, 20036, USA.
authors: Eileen
authors: E
authors: Resnick
authors: Isis Research Network on Musculoskeletal Health, Society for Women's Health Research, 1025 Connecticut Avenue, NW Suite 601, Washington, DC, 20036, USA.
authors: Karen J
authors: KJ
authors: Berkley
authors: Isis Research Network on Musculoskeletal Health, Society for Women's Health Research, 1025 Connecticut Avenue, NW Suite 601, Washington, DC, 20036, USA.
authors: Kathleen A
authors: KA
authors: Sluka
authors: University of Pittsburgh and Pittsburgh VA Healthcare System, Pittsburgh, PA, USA.|Epidemiology, and Clinical and Translational Science Division of Rheumatology and Clinical Immunology, University of Pittsburgh School of Medicine, University of Pittsburgh Arthritis Institute, Pittsburgh, USA.
authors: C Kent
authors: CK
authors: Kwoh
authors: Isis Research Network on Musculoskeletal Health, Society for Women's Health Research, 1025 Connecticut Avenue, NW Suite 601, Washington, DC, 20036, USA.
authors: Laura L
authors: LL
authors: Tosi
authors: Isis Research Network on Musculoskeletal Health, Society for Women's Health Research, 1025 Connecticut Avenue, NW Suite 601, Washington, DC, 20036, USA.|Mayo Clinic, 4500 San Pablo Road, Jacksonville, Florida, USA.
authors: Mary I
authors: MI
authors: O'Connor
authors: Isis Research Network on Musculoskeletal Health, Society for Women's Health Research, 1025 Connecticut Avenue, NW Suite 601, Washington, DC, 20036, USA.
authors: Richard D
authors: RD
authors: Coutts
authors: Isis Research Network on Musculoskeletal Health, Society for Women's Health Research, 1025 Connecticut Avenue, NW Suite 601, Washington, DC, 20036, USA.
authors: Wendy M
authors: WM
authors: Kohrt
references: Ann Rheum Dis. 1996 Sep;55(9):673-6
references: 8882148
references: J Endocrinol. 2007 Jun;193(3):421-33
references: 17535880
references: Ann Rheum Dis. 2004 Mar;63(3):269-73
references: 14962961
references: Ann N Y Acad Sci. 2010 Mar;1192:230-7
references: 20392241
references: J Oral Maxillofac Surg. 2006 Apr;64(4):600-9
references: 16546639
references: Steroids. 2011 Aug;76(9):903-9
references: 21371489
references: J Rheumatol. 2007 Jan;34(1):130-9
references: 17117483
references: Am J Sports Med. 2006 Dec;34(12):1948-52
references: 16861578
references: Am J Physiol Regul Integr Comp Physiol. 2008 Nov;295(5):R1425-30
references: 18784332
references: Am J Physiol Regul Integr Comp Physiol. 2005 Jul;289(1):R15-22
references: 15790748
references: J Surg Res. 2007 Jun 1;140(1):55-66
references: 17275032
references: Histochem Cell Biol. 2012 Jan;137(1):79-95
references: 22057437
references: Endocrinology. 2004 Aug;145(8):3788-95
references: 15131017
references: Genet Med. 2010 Oct;12(10):597-605
references: 20847697
references: Arthritis Rheum. 2004 Oct;50(10):3145-52
references: 15476248
references: Eur J Med Res. 1999 Sep 9;4(9):357-60
references: 10477499
references: Bone. 2006 Sep;39(3):460-9
references: 16713415
references: J Mol Endocrinol. 2008 Nov;41(5):263-75
references: 18772268
references: Cancer Res. 2009 Jan 1;69(1):16-22
references: 19117982
references: Connect Tissue Res. 1994;30(4):277-94
references: 7956206
references: Am J Sports Med. 2009 Jun;37(6):1169-77
references: 19289541
references: J Gend Specif Med. 2000 Oct;3(7):58-64
references: 11252928
references: Mol Endocrinol. 2003 May;17(5):870-81
references: 12554777
references: PM R. 2012 May;4(5 Suppl):S169-73
references: 22632696
references: Knee Surg Sports Traumatol Arthrosc. 2009 Jul;17(7):786-94
references: 19360401
references: Biochim Biophys Acta. 2009 Mar;1792(3):211-20
references: 19185056
references: Curr Opin Rheumatol. 2011 Sep;23(5):471-8
references: 21788902
references: Endocrinology. 2006 Apr;147(4):2028-34
references: 16410299
references: Maturitas. 2011 Jun;69(2):141-56
references: 21481553
references: Cancer Res. 2009 Mar 15;69(6):2305-13
references: 19244107
references: J Athl Train. 1999 Apr;34(2):86-92
references: 16558564
references: Hum Reprod Update. 2000 May-Jun;6(3):225-36
references: 10874567
references: J Periodontol. 2009 Oct;80(10):1622-30
references: 19792852
references: Endocr Rev. 2002 Feb;23(1):90-119
references: 11844745
references: Clin Biomech (Bristol, Avon). 2007 Jan;22(1):1-13
references: 17056168
references: J Anat. 1990 Oct;172:69-79
references: 2272910
references: Br J Sports Med. 2012 Aug;46(10):696-8
references: 21908882
references: Mol Endocrinol. 2004 Dec;18(12):2854-65
references: 15231873
references: Knee Surg Sports Traumatol Arthrosc. 2008 May;16(5):442-8
references: 18292988
references: Bone. 2007 Jan;40(1):111-21
references: 16973427
references: Am J Sports Med. 2010 Jul;38(7):1334-42
references: 20410376
references: Osteoarthritis Cartilage. 2008 May;16(5):533-41
references: 18280756
references: Acta Orthop Suppl. 2010 Feb;81(340):1-53
references: 21110779
references: Osteoporos Int. 2010 Mar;21(3):365-72
references: 19495826
references: Arthritis Rheum. 2001 Jun;44(6):1237-47
references: 11407681
references: Am J Physiol Endocrinol Metab. 2007 Jul;293(1):E410-5
references: 17473054
references: Rheumatology (Oxford). 2008 Dec;47(12):1785-91
references: 18927192
references: Am J Sports Med. 2010 Oct;38(10):2025-33
references: 20595554
references: Br J Sports Med. 2010 Jan;44(1):21-5
references: 19952376
references: Immunol Res. 2006;34(3):177-92
references: 16891670
references: J Steroid Biochem Mol Biol. 2012 Oct;132(1-2):15-23
references: 22207084
references: Biochim Biophys Acta. 2006 Apr;1763(4):381-92
references: 16713447
references: J Endocrinol. 2006 Sep;190(3):837-46
references: 17003284
references: Rheumatology (Oxford). 2004 Sep;43(9):1194-5
references: 15317957
references: Baillieres Best Pract Res Clin Rheumatol. 2000 Jun;14(2):345-61
references: 10925749
references: Breast Cancer Res Treat. 2012 Jan;131(2):473-81
references: 21390495
references: Minn Med. 2007 Jun;90(6):38-40
references: 17621921
references: Endocrinology. 2006 Mar;147(3):1386-95
references: 16339199
references: Ann Anat. 2011 Feb 20;193(1):23-9
references: 20971625
references: Ann Endocrinol (Paris). 2003 Apr;64(2):95-107
references: 12773942
references: Bone. 2002 Jan;30(1):57-63
references: 11792565
references: Proc Biol Sci. 2012 Jan 7;279(1726):202-8
references: 21632627
references: Br J Sports Med. 2009 Mar;43(3):174-9
references: 18728055
references: Oral Dis. 2006 May;12(3):329-42
references: 16700745
references: Sports Med. 2006;36(10):847-62
references: 17004848
references: Psychoneuroendocrinology. 2010 Aug;35(7):1063-73
references: 20137860
references: Cell Tissue Res. 2010 Nov;342(2):283-93
references: 20941509
references: Eur J Appl Physiol. 2011 Sep;111(9):2281-94
references: 21331628
references: Steroids. 2008 Oct;73(9-10):953-60
references: 18249430
references: Osteoarthritis Cartilage. 1999 Nov;7(6):560-6
references: 10558854
references: Br J Sports Med. 2010 Sep;44(12):848-55
references: 19158132
references: Ann Rheum Dis. 2005 Mar;64(3):504-5
references: 15708907
references: J Androl. 2006 Sep-Oct;27(5):671-8
references: 16728719
references: Arthritis Rheum. 2004 Aug;50(8):2640-4
references: 15334479
references: J Cell Biochem. 2005 May 1;95(1):108-19
references: 15723286
references: Arq Bras Endocrinol Metabol. 2006 Aug;50(4):720-34
references: 17117297
references: J Rheumatol. 2003 Apr;30(4):799-803
references: 12672202
references: Arthritis Rheum. 2010 Apr;62(4):1077-87
references: 20131243
references: J Orthop Res. 2011 Oct;29(10):1563-71
references: 21469181
references: Tissue Eng Part B Rev. 2012 Jun;18(3):181-202
references: 22070552
references: Menopause. 2009 Jul-Aug;16(4):666-70
references: 19598333
references: J Clin Endocrinol Metab. 2003 Feb;88(2):871-8
references: 12574227
references: Osteoarthritis Cartilage. 2005 Apr;13(4):330-7
references: 15780646
references: Am J Sports Med. 2009 Mar;37(3):588-98
references: 19174550